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Germinal Centers (germinal + center)
Terms modified by Germinal Centers Selected AbstractsThe Allantoic Core Domain: New insights into development of the murine allantois and its relation to the primitive streakDEVELOPMENTAL DYNAMICS, Issue 3 2009Karen M. Downs Abstract The whereabouts and properties of the posterior end of the primitive streak have not been identified in any species. In the mouse, the streak's posterior terminus is assumed to be confined to the embryonic compartment, and to give rise to the allantois, which links the embryo to its mother during pregnancy. In this study, we have refined our understanding of the biology of the murine posterior primitive streak and its relation to the allantois. Through a combination of immunostaining and morphology, we demonstrate that the primitive streak spans the posterior extraembryonic and embryonic regions at the onset of the neural plate stage (,7.0 days postcoitum, dpc). Several hours later, the allantoic bud emerges from the extraembryonic component of the primitive streak (XPS). Then, possibly in collaboration with overlying allantois-associated extraembryonic visceral endoderm, the XPS establishes a germinal center within the allantois, named here the Allantoic Core Domain (ACD). Microsurgical removal of the ACD beyond headfold (HF) stages resulted in the formation of allantoic regenerates that lacked the ACD and failed to elongate; nevertheless, vasculogenesis and vascular patterning proceeded. In situ and transplantation fate mapping demonstrated that, from HF stages onward, the ACD's progenitor pool contributed to the allantois exclusive of the proximal flanks. By contrast, the posterior intraembryonic primitive streak (IPS) provided the flanks. Grafting the ACD into TC/TC hosts, whose allantoises are significantly foreshortened, restored allantoic elongation. These results revealed that the ACD is essential for allantoic elongation, but the cues required for vascularization lie outside of it. On the basis of these and previous findings, we conclude that the posterior primitive streak of the mouse conceptus is far more complex than was previously believed. Our results provide new directives for addressing the origin and development of the umbilical cord, and establish a novel paradigm for investigating the fetal/placental relationship. Developmental Dynamics 238:532,553, 2009. © 2009 Wiley-Liss, Inc. [source] Fine-needle aspiration cytology of Castleman disease: Case report with review of the literatureDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2008Majorie Deschênes M.D. Abstract Organs involved by Castleman disease (CD) may be investigated by fine-needle aspiration cytology. No specific cytomorphological criteria are currently described for a definitive diagnosis. The cytological features of three fine-needle aspirations from three different lymph nodes of a patient with histologically confirmed CD of the hyaline-vascular type are herein reported, with a review of the literature. The fine-needle aspirations showed branching capillaries associated with fragments of germinal center. Review of the literature yielded 12 other case reports with over half describing similar findings. Because branching hyalinized small blood vessels penetrating follicular germinal center are characteristic of CD of the hyaline-vascular type on histology, this finding in fine-needle aspirates should raise that diagnostic possibility. Diagn. Cytopathol. 2008. © 2008 Wiley-Liss, Inc. [source] Lymphocyte-expressed BILL-cadherin/cadherin-17 contributes to the development of B cells at two stagesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Kazuo Ohnishi Abstract The gene encoding BILL-cadherin/cadherin-17, a nonclassical cadherin expressed on B lymphocytes in a stage-and-site-specific manner, was inactivated by targeted disruption of its transmembrane/cytoplasmic portion-encoding parts. BILL-cadherin deficiency caused a threefold proB cell accumulation, as well as a reduction to half of the numbers of immature B cells in bone marrow. In spleen, CD21hiCD23lo marginal zone B cells were found reduced and the structure of the marginal zone was impaired. In addition, the size and number of germinal center as well as the number of PNA+ cells were significantly reduced in BILL-cadherin-deficient mice. In the peritoneal cavity of mutant mice IgM+Mac-1+CD5+ B1a cell, that express high BILL-cadherin in wild-type mice, was also reduced in number. The IgG1 and IgG3 antibody response to the T-independent antigen, TNP-Ficoll, was impaired in the mutant mice. These results indicate that BILL-cadherin participates in B lymphocyte development at least at two stages, first at the transition of pro/preB-I cells to preB-II cells possibly in association with surrogate light chain in bone marrow, and later at the point of development, accumulation and reactiveness of immature B cells in spleen. [source] Fc,RII expression on follicular dendritic cells and immunoreceptor tyrosine-based inhibition motif signaling in B,cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2004Yüksel Aydar Abstract Immune complexes (IC) initiate immunoreceptor tyrosine-based inhibition motif (ITIM) signaling and inhibit B,cell activation by coligating B,cell receptor for antigen (BCR) and Fc,RII. Nevertheless, IC on follicular dendritic cells (FDC) stimulate rapid germinal center (GC) B,cell proliferation suggesting that interactions between IC and FDC render IC capable of B,cell activation. Tounderstand this, we studied the kinetics of FDC Fc,RII and complement receptors,1 and,2 (CR1&2) expressions during the GC reaction and determined whether FDC Fc,RII could bind Fc in IC and block ITIM signaling. Mice were immunized with sheep red blood cells (SRBC), and CR1&2 and Fc,RII levels in FDC reticula were monitored. The role of FDC Fc,RII was studied using anti-BCR-stimulated A20 cells. Levels of FDC Fc,RII in spleens of SRBC-injected mice increased within 24,h and were dramatically increased (,50-fold) on days,3 and,5. In contrast, CR1&2 levels increased less than twofold. Addition of normal FDC, but not FDC lacking Fc,RII, reduced and reversed anti-BCR-induced SH2 domain-containing inositol phosphatase (SHIP)-1 phosphorylation in A20 cells. FDC wereable to induce normal recall responses even after overnight incubation of the lymphocytes with IC to stimulate ITIM signaling. Engagement of Ig Fc with numerous Fc,RII on FDC appears to minimize IC-induced ITIM signaling. Thus, rapid up-regulation of FDC Fc,RII may explain why poorly immunogenic IC are rendered highly immunogenic when presented by FDC in GC. [source] One cell, one antibody: prelude and aftermathIMMUNOLOGICAL REVIEWS, Issue 1 2002G. J. V. Nossal Summary: This essay seeks to summarize one scientist's pilgrim's progress through the world of antibody formation, attempting to capture the flavor of problems as encountered within their times. It seeks to portray a world where the direct template hypothesis ruled the day, where the function of lymphocytes was unknown, let alone the difference between T and B cells, and where antibody genes were but a dream. Struggles to establish the credentials of the clonal selection hypothesis are presented in some detail, as are the implications which followed the ,one cell , one antibody' discovery. The other two main preoccupations of the author are presented more briefly, namely the essential features of the germinal center and the cellular basis of immunological tolerance within the B lymphocyte compartment. Naturally, the experiments become more sophisticated as both knowledge and technology mature. A continuing thread within the unfolding story is that one must not shy away from developing new techniques when problems demand them. [source] Cutaneous Rosai-Dorfman DiseaseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005L. Lin Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare benign disease of unknown etiology that involves the cervical lymph nodes. Histologic findings include emperiopolesis of lymphocytes and S-100 protein positivity. Extranodal involvement occurs in 30,40% of cases, often involving skin. However, cutaneous Rosai-Dorfman disease without lymph node involvement is uncommon. We describe a case of cutaneous Rosai-Dorfman disease and discuss its clinical and histopathologic findings. A 69-year-old Caucasian male presented with a two-year history of a slowly enlarging violaceous mass on the mid-upper abdomen. He had a history of renal cell carcinoma two-year ago and was asymptomatic without any systemic symptoms. Physical examination revealed a large, violaceous mass of mid-upper abdomen with several violaceous nodules surrounding the periphery. There was no palpable lymphadenopathy. Punch biopsy showed diffuse dermal infiltrates composed of central xanthomatous cells surrounded by lymphoplasmacytic cells. Focal germinal center was noted. Immunostaining revealed strong S-100 and CD68 reactivity of central xanthomatous cells and kappa and lambda polyclonal lymphoplasmacytic cells. Special stains for infectious disorder were negative. Cutaneous Rosai-Dorfman disease is a benign reactive process, often under-recognized due to lack of systemic symptoms and lymphadenopathy. A high index of diagnostic awareness is required for its recognition. [source] SHP-1 expression in primary central nervous system B-cell lymphomas in immunocompetent patients reflects maturation stage of normal B cell counterpartsPATHOLOGY INTERNATIONAL, Issue 9 2004Yasuo Sugita SHP-1 is an important negative regulator involved in signaling through receptors for cytokine/growth factors, and differential patterns of SHP-1 expression in several types of B-cell lymphomas closely resemble the patterns seen in their normal B cell counterparts. In an effort to elucidate the origin of primary central nervous system lymphomas (PCNSL), the present study assessed 32 cases of PCNSL. Tumors were subclassified according to WHO classification and were evaluated by immunohistochemistry for expression of antigens associated with germinal center (GC) (CD10, Bcl-6) and non-GC stages (SHP-1, CD138). Twenty-nine cases showed diffuse large-cell centroblastic morphology, whereas three cases showed diffuse large-cell immunoblastic morphology. The immunophenotypes of PCNSL were as follows: SHP-1+/Bcl-6,/CD10,/CD138, (12 of 32 cases); SHP-1+/Bcl-6+/CD10,/CD138, (15 of 32 cases); SHP-1+/Bcl-6+/CD10+/CD138, (two of 32 cases); SHP-1+/Bcl-6,/CD10+/CD138, (one of 32 cases); and SHP-1,/Bcl-6,/CD10,/CD138, (two of 32 cases). These results indicate that PCNSL might be distinct lymphomas that originate from a late germinal center to an early postgerminal center. [source] HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric Castleman's diseasePATHOLOGY INTERNATIONAL, Issue 9 2001Tetsuji Suda Multicentric Castleman's disease (MCD) is a clinicopathologically defined entity characterized by systemic lymphadenopathy with unique pathomorphology such as angiosclerosis, blood vessel proliferation in and around follicles, and plasmacytosis. While its pathogenesis has remained unclarified for many years, identification of the human herpesvirus 8 (HHV-8) in at least some MCD cases has opened new perspectives in this field. Because previous reports have described many inconsistencies regarding HHV-8 positivity in MCD, we intended to clarify this issue by the introduction of more convincing methodologies. For this investigation, we introduced two antibodies produced in our laboratories that recognize a latent gene product ORF73 and a lytic gene product ORF59, together with two well-recognized methods, in situ hybridization for the detection of lytic phase transcript T1.1/nut -1, and genomic polymerase chain reaction (PCR). Eighty-two cases of MCD were collected from Japan (n= 75) and France (n= 7). In three cases, the patients were suffering from acquired immunodeficiency syndrome (AIDS). Immunohistochemistry and in situ hybridization showed identical results: only three out of 82 cases were positively stained, and all the positive cases were found to be the patients with AIDS. Genomic PCR was done in 43 cases, and only one case produced positive results: the only AIDS case among the 43 cases studied by genomic PCR. Histopathologically, the HHV-8-positive cases showed the highest intensity of angiosclerosis and germinal center / perifollicular vascular proliferation, while plasmacytosis was not severe in the HHV-8-positive cases. Some of the HHV-8-negative MCD cases displayed similar histopathology, but at a far less intense level, except for the plasmacytosis. These results suggest that: (i) all three of the HHV-8-positive MCD patients in the present group are the patients with AIDS; and (ii) HHV-8-positive MCD patients develop typical but marked angiosclerosis and vascular proliferation that might be differentiated from HHV-8-negative MCD patients, who showed far less intense changes. [source] Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French,American,British (FAB) international study group,PEDIATRIC BLOOD & CANCER, Issue 3 2008Rodney R. Miles MD Abstract Background Diffuse large B-cell lymphoma (DLBCL) makes up 10,20% of pediatric non-Hodgkin lymphoma, and these patients have a significantly better prognosis than adults with DLBCL. The difference in prognosis may be related to clinical, phenotypic, and/or biological differences between adult and pediatric DLBCL. In adult DLBCL, the germinal center (GC) phenotype is associated with a better prognosis than the activated B-cell (ABC) phenotype. However, a high proliferative index and expression of Bcl2 and c-Myc protein have all been associated with worse outcomes. While multiple studies have addressed the phenotype and expression patterns of adult DLBCL, relatively little is known about these biological variables in pediatric DLBCL. The goal of this study was to investigate the proliferative index, the relative frequencies of the GC and non-GC subtypes, and the expression of Bcl2 and c-Myc protein in a cohort of children with DLBCL treated in a uniform manner. Procedure We performed immunohistochemistry (IHC) for MIB1, CD10, Bcl6, MUM1, Bcl2, and c-Myc on DLBCL tissue from children treated uniformly in the FAB LMB96 trial (SFOP LMB96/CCG5961/UKCCSG/NHL 9600). Results Compared to published adult DLBCL studies, pediatric DLBCL demonstrated moderate to high proliferation rates (83%), increased c-Myc protein expression (84%), decreased Bcl2 protein expression (28%), and an increased frequency of the GC phenotype (75%). Conclusions These findings suggest that there are significant biologic differences between pediatric and adult forms of DLBCL, which may contribute to the superior prognosis seen in the pediatric population relative to adult disease. Pediatr Blood Cancer 2008;51:369,374. © 2008 Wiley-Liss, Inc. [source] Differentiating germinal center-derived lymphomas through their cellular microenvironment,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009Antonino Carbone Recent studies on normal and malignant B-cells have provided evidence that the germinal center (GC) of lymphoid follicles exerts a role in B-cell physiology and malignancy. GC-derived lymphomas include both B-cell and T-cell lymphomas. Remarkably, tumor cells of GC-derived lymphomas proliferate in close association with cellular environment that retains key features of normal GC cellular microenvironment. Neoplastic follicles in follicular lymphoma contain, in addition to follicular dendritic cells (FDC) other non-neoplastic cells including macrophages and GC T-cells. In addition to aggregates of FDCs, the background infiltrate of nodular lymphocyte predominant Hodgkin lymphoma includes small B-cells, T-cells, and histiocytes. Typically, most of the lymphocyte predominant (LP) cells are ringed by CD3+/CD4+ T-cells expressing CD57, PD1, BCL6, and MUM1/IRF4. By contrast, Reed,Sternberg cells of classic Hodgkin lymphoma (cHL) are surrounded by CD3+/CD4+ T-cells expressing CD40L. Unlike cHL and other peripheral T-cell lymphomas, the AITL microenvironment characteristically contain a prominent proliferation of high endothelial venules and FDC. Thus, these findings shed new light on the characterization of GC-derived lymphomas and may help in the differential diagnosis and acknowledge several novel pathogenetic mechanisms on these lymphomas. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Follicular lymphoid hyperplasia of the oral cavity representing progressive transformation of germinal center,APMIS, Issue 3 2005Case report Follicular lymphoid hyperplasia (FLH) of the oral cavity is a rare and poorly understood lymphoproliferative disorder. We present a case of FLH of the oral cavity presenting with progressive transformation of germinal center (PTGC). The patient was a 49-year-old Japanese woman presenting with a hard mass in the right cheek. The resected specimen contained numerous lymphoid follicles with active germinal centers and a portion of the lymphoid follicles exhibited PTGC. The PTGCs contained a few large lymphoid cells resembling lymphocytic and histiocytic Reed-Sternberg cells of nodular lymphocyte-predominant Hodgkin lymphoma. The PTGC was surrounded by groups of epithelioid cells. In situ hybridization studies demonstrated strong expression of Epstein-Barr virus (EBV)-encoded small RNA in scattered large lymphoid cells in the PTGC. Although the etiology of FLH of the oral cavity remains unclear, the present case suggests that a subset of FLH of the oral cavity appears to be an EBV-associated lymphoproliferative disorder. [source] Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in elderly patients Report of three casesAPMIS, Issue 12 2003MASARU KOJIMA Three cases of Epstein-Barr virus (EBV)-related lymphoproliferative disorders in elderly patients showing autoimmune disease-associated lymphadenopathy-like clinicopathological findings have been reported. Clinically, they were characterized by systemic lymphadenopathy, "B" symptoms, polyclonal hypergammaglobulinemia, elevated serum LDH and transient presence of various autoantibodies, and absence of atypical lymphocytosis in peripheral blood. One case was associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, they exhibited numerous lymphoid follicles with hyperplastic germinal centers and atypical interfollicular widening with prominent vascular proliferation. In the paracortical area, there was a mixed infiltrate comprising small to medium-sized lymphocytes and plasma cells, and variable numbers of eosinophils and T- and B-immunoblasts. In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center as well as in the interfollicular area. Polymerase chain reaction demonstrated that neither clonal rearrangement of T-cell receptor ,-gene nor immunoglobulin heavy-chain rearrangement was detected in two of the cases examined. Although acute EBV infection rarely occurs in older adults, EBV related to reactive lymphoproliferative disorder should be added to the differential diagnosis of autoimmune disease-associated lymphadenopathy and node-based peripheral T-cell lymphoma in elderly patients. [source] Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapyARTHRITIS & RHEUMATISM, Issue 9 2007Jennifer H. Anolik Objective Recent data suggest that the reconstituting peripheral B cell compartment after B cell depletion therapy may be functionally immature, with a preponderance of transitional B cells and a paucity of memory B cells. This study was undertaken to determine the magnitude, duration, and cause of these defects in rituximab-treated systemic lupus erythematosus (SLE) patients. Methods Fifteen patients with SLE previously treated with rituximab as part of a phase I/II dose-escalation study were evaluated during a long-term followup (mean followup period 41 months). B cells from peripheral blood and tonsils were assessed using multicolor flow cytometry, and their developmental pathway was classified based on the expression of defined surface markers. Results Reconstitution of peripheral blood CD27+ memory B cells was delayed for several years after B cell depletion therapy in a subset of patients with prolonged clinical responses and autoantibody normalization. This delay correlated with the degree of expansion of B cells of a transitional phenotype during the B cell reconstitution phase (P = 0.005) and the absence of baseline autoantibodies directed against extractable nuclear antigens (RNP, Sm, Ro antigen, La antigen). Despite the paucity of peripheral blood memory cells and the prolonged expansion of functionally immature transitional B cells, tonsil biopsy tissues revealed active germinal center (GC) reactions, but with decreased Fc receptor homolog 4,positive memory B cells. Conclusion These results suggest heterogeneity in the B cell depletion and reconstitution process that impacts clinical and immunologic outcomes in SLE. The presence of GC reactions, but with altered memory B cell subpopulations in tonsils, suggests that peripheral blood memory cell reconstitution lags behind a slow secondary lymphoid tissue recovery, with important implications for immunologic competence and tolerance. [source] Decreased expression of germinal center,associated nuclear protein is involved in chromosomal instability in malignant gliomasCANCER SCIENCE, Issue 11 2009Kazutaka Ohta Malignant glioma (MG) is highly proliferative and invasive, with the malignant characteristics associated with aneuploidy and chromosomal instability (CIN). Here, we found that the level of germinal center,associated nuclear protein (GANP), a mammalian homologue of yeast Sac3, was markedly decreased in MGs with a poor prognosis; and thus we explored the effect of its decrease on cell-cycle progression of MG cell lines. Glioblastomas showed a significantly lower level of ganp mRNA than anaplastic astrocytomas, as measured by real-time reverse transcription-PCR, in 101 cases of adult MG. MGs of ganpLow expression displayed more malignant characteristics, with loss of heterozygosity on chromosome 10, epidermal growth factor receptor gene amplification, and significantly poorer prognosis than the ganpHigh group. Human diploid fibroblasts depleted of ganp mRNA by the RNA interference (RNAi) method showed a decreased percentage of S-phase cells and a cellular-senescence phenotype. MG cell lines harboring abnormalities of various cell-cycle checkpoint molecules displayed slippage of mitotic checkpoints and an increased proportion of hyperploid cells after ganp RNAi-treatment. These results suggest that GANP protects cells from cellular senescence caused by DNA damage and that a significant decrease in GANP expression leads to malignancy by generating hyperploidy and CIN. (Cancer Sci 2009); 00: 000,000) [source] SMALL EARLY GASTRIC CANCER OCCURRING IN A YOUNG WOMAN WITH NODULAR GASTRITISDIGESTIVE ENDOSCOPY, Issue 2 2007Shuji Kochi We found a small gastric cancer in a 25-year-old woman with nodular gastritis. Endoscopically, the cancer was identified as a whitish area in the gastric antrum. There was also a miliary pattern in the gastric antrum and corpus. In addition, serology and histology revealed the patient to have been infected by Helicobacter pylori. Histological examination of the resected stomach showed that the cancer was poorly differentiated adenocarcinoma with signet-ring cell restricted to the mucosal layer. In the surrounding mucosa, there were chronic inflammatory cell infiltrates and enlarged lymphoid follicles with germinal centers. Our case suggests that nodular gastritis may be at a high risk for the development of gastric cancer of poorly differentiated type. [source] The germinal center response is impaired in the absence of T cell-expressed CXCR5EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Carrie Abstract Germinal centers support the differentiation of memory B cells and long-lived antibody-secreting cells during infection or upon vaccination. Here, we constructed mice with T cells that selectively lack the chemokine receptor CXCR5 to determine if expression of this receptor by T cells is mandatory for germinal center formation and function. In these animals, germinal centers that are properly localized in B cell follicles and contain T cells do form after immunization with a thymus-dependent antigen. However, fewer and smaller germinal centers form, resulting in a significant reduction in the frequency of germinal center B cells. The defect in germinal center formation is paralleled by decreased frequencies of isotype-switched antibody-secreting cells in the spleen and bone marrow and reduced serum concentrations of total and high-affinity hapten-specific IgG1. The results demonstrate that although CXCR5-dependent T cell positioning is important for maximal induction and expansion of germinal centers, stimulation of isotype class switching, and development of antibody-secreting cells that seed the spleen and bone marrow, it is not absolutely required for the formation and function of follicular germinal centers. [source] Toll-like receptor engagement stimulates anti-snRNP autoreactive B cells for activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2006Chuanlin Ding Abstract Autoreactive B cells are the source of pathogenic autoantibodies (autoAb) in systemic lupus erythematosus (SLE). Previous studies have demonstrated that anti-small nuclear ribonucleoprotein particles (snRNP) B cells from normal background mice tolerize T cells in the periphery and do not secrete autoAb. In this study, we examined whether these anti-snRNP B cells can be activated for autoAb production by the engagement of Toll-like receptors (TLR). Anti-snRNP B cells proliferated vigorously and secreted abundant anti-snRNP autoAb upon exposure to CpG or polyriboinosinic polyribocytidylic acid [poly,(I:C)] in vitro. In addition, the costimulatory molecules CD80 and CD86 were up-regulated. While both anti-snRNP B cells and wild-type B cells produced similar levels of IL-6 and IL-10, anti-snRNP B cells secreted predominately IFN-, in response to CpG or poly,(I:C) stimulation. Furthermore, we showed that in vivo engagement of TLR stimulated immature anti-snRNP B cells to further differentiate and produce autoAb and form germinal centers. The activated anti-snRNP B cells became expanded and migrated into the T-B cell interface. Moreover, TLR engagement directly or indirectly activated autoreactive B cells via a CD4 T cell-independent manner. These results provide in vitro and in vivo evidence that BCR/TLR co-engagement promotes the activation of anti-snRNP B cells for autoAb production. [source] Polymerase,, is up-regulated during the T,cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblastsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2005Daniel Lucas Abstract Mammalian DNA polymerase,, (Pol,), preferentially expressed in secondary lymphoid organs, is shown here to be up-regulated in germinal centers after immunization. Alternative splicing appears to be part of Pol, regulation during an immune response. We generated Pol,-deficient mice that are viable and show no anatomical malformation or serious alteration in lymphoid populations, with the exception of an underrepresentation of the B,cell compartment. Young and aged homozygous Pol,,/, mice generated similar immune responses after immunization with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken gammaglobulin (CGG), compared with their wild-type littermates. Nonetheless, the kinetics of development of the centroblast population showed significant differences. Hypermutation analysis of the rearranged heavy chain intron region in centroblasts isolated from NP-CGG-immunized Pol,,/, mice showed a similar quantitative and qualitative somatic mutation spectrum, but a lower representation of heavily mutated clones. These results suggest that although it is not a critical partner, Pol, modulates the in vivo somatic hypermutation process. [source] Castleman's disease with numerous mantle zone lymphocytes with clear cytoplasm involving the skin: case reportJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2009Dario Tomasini Castleman's disease (CD) is an unusual lymphoid hyperplasia occurring in the mediastinal lymph nodes and, less frequently, in the neck lymph nodes. CD is classified clinically into a unicentric and a multicentric type, whereas three histomorphological variants are recognized: the hyaline vascular type, the intermediate type and the plasma cell type. We report the clinical and pathological features of a 54-year-old female suffering with multiple sclerosis and developing a lymph node hyaline-vascular type CD relapsing in the skin after 24 months. Histological features showed a nodular dermatitis with atrophic germinal centers and an ,onion skin' rimming of lymphocytes in the mantle zone with numerous mantle zone lymphocytes with clear cytoplasm, with a CD20+, CD79a+, IgM+, IgG,, IgA,, CD5,, CD10,, CD43,, CD45RO,, bcl-2+ and bcl-6, phenotype with polytypic nature supporting the diagnosis of lymphoid variant of hyaline-vascular CD. This case shows that skin CD recapitulates all the histological variants of lymph node CD. Considering the many similarities between the present case and the primary cutaneous marginal zone lymphoma, it is important to bear in mind this atypical lymphoproliferative disorder in order to avoid overdiagnosis and overtreatment. [source] Lupus erythematosus panniculitis (lupus profundus): Clinical, histopathological, and molecular analysis of nine casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2005Cesare Massone Background:, The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Methods:, We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20,71 years). Results:, Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance of ,/,-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-, gene showed a polyclonal smear in all cases. Conclusions:, Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-, gene rearrangement. [source] Morphological spectrum of cyclin D1-positive mantle cell lymphoma: Study of 168 casesPATHOLOGY INTERNATIONAL, Issue 10 2001Yasushi Yatabe Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium, large (13.2%) and large (6.6%) cells. Pleomorphic and blastic / blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia / small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features. [source] Lymphoid hyperplasia of the large intestine: A case report with immunohistochemical and gene analysisPATHOLOGY INTERNATIONAL, Issue 9 2000Sakae Nagaoka A case of lymphoid hyperplasia arising in the large intestine of a 54-year-old woman is described. Barium enema X-ray and colonoscopic examination revealed multiple small polyps in the right side of the colon. Pathological findings from forceps biopsy revealed similar features to a mucosa-associated lymphoid tissue (MALT) lymphoma. A right hemicolectomy with mesenteric lymph node dissection was carried out. Histological sectioning demonstrated hypertrophic lymphoid follicles with well-formed germinal centers. Occasionally, lymphocytes infiltrated the crypts, in a way similar to that found in lymphoepithelial lesions, which was suggestive of a MALT lymphoma diagnosis. Cryptitis was also observed in the lamina propria. Immunohistochemically, proliferating lymphocytes were positive for CD20 (L26) and negative for CD45RO (UCHL-1). Analyses of immunoglobulin gene (IgHJH) rearrangement could not detect any monoclonality in these cells. These findings suggested that the present case should be categorized as lymphoid hyperplasia rather than lymphoma. [source] The Microanatomy of the Palatine Tonsils of the One-Humped Camel (Camelus dromedarius)THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2009Mohamed Zidan Abstract Tonsils form a first line of defense against foreign antigens and are also a route of entry and a replication site for some pathogens. The palatine tonsils are the largest of all the tonsils. Despite their general importance, little is known about the microanatomy of the palatine tonsils of the one-humped camel. Palatine tonsils of 10 clinically healthy male camels were obtained directly after slaughtering for human consumption. The tonsils were examined macroscopically and by light, scanning, and transmission electron microscopy. Palatine tonsils had the unique form of several spherical macroscopic nodules protruding into the pharyngeal lumen. These spherical masses were numerous and close together in the lateral oropharyngeal wall, with a few solitary nodules in the dorsal wall. Each nodule had one or two apical openings to crypts, and was enclosed by an incomplete connective tissue capsule and covered apically with stratified squamous keratinized epithelium. The tonsillar crypt was lined with stratified squamous non keratinized epithelium. Several lymphocytes infiltrated the epithelial layer, forming patches of reticular epithelium. Lymphoid follicles with obvious germinal centers extended under the epithelial surface. Diffusely localized lymphocytes were seen in the interfollicular region. High endothelial venules, dendritic cells, macrophages, and plasma cells were observed among these lymphocytes. The unique arrangement of palatine tonsils in separate units with individual crypts results in a very large surface exposed to antigen and indicates a significant immunological role of palatine tonsils in the camel. Anat Rec, 292:1192,1197, 2009. © 2009 Wiley-Liss, Inc. [source] Epstein-Barr virus persistence and reactivation in myasthenia gravis thymusANNALS OF NEUROLOGY, Issue 6 2010Paola Cavalcante PhD Objective Increasing evidence supports a link between Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic human herpesvirus, and common B-cell,related autoimmune diseases. We sought evidence of EBV infection in thymuses from patients with myasthenia gravis (MG), an autoimmune disease characterized by intrathymic B-cell activation. Methods Seventeen MG thymuses (6 follicular hyperplastic, 6 diffuse hyperplastic, 5 involuted) and 6 control thymuses were analyzed using in situ hybridization for EBV-encoded small RNAs (EBERs), immunohistochemistry for EBV latent and lytic proteins, and polymerase chain reaction for EBV DNA and mRNA. Results All 17 MG thymuses showed evidence of active EBV infection, whereas none of the control thymuses were infected. Cells expressing EBERs (12 of 17) and EBV latency proteins (EBNA2, LMP1, and LMP2A) (16 of 17) were detected in medullary infiltrates and in germinal centers. Cells expressing early (BFRF1, BMRF1) and late (p160, gp350/220) lytic phase EBV proteins were present in 16 MG thymuses. Latency (EBNA1, LMP2A) or lytic (BZLF1) transcripts (often both) were present in all MG thymuses, and EBV DNA (LMP1 gene) was detected in 13 MG thymuses. We also found CD8+ T cells, CD56 + CD3-natural killer cells, and BDCA-2+ plasmacytoid dendritic cells in immune infiltrates of MG thymuses, but not germinal centers, suggesting an attempt of the immune system to counteract EBV infection. Interpretation Dysregulated EBV infection in the pathological thymus appears common in MG and may contribute to the immunological alterations initiating and/or perpetuating the disease. ANN NEUROL 2010;67:726,738 [source] CCL21 overexpressed on lymphatic vessels drives thymic hyperplasia in myasthenia,ANNALS OF NEUROLOGY, Issue 4 2009Sonia Berrih-Aknin PhD Objective Myasthenia gravis (MG), a neuromuscular disease mediated by anti-acetylcholine receptor (AChR) autoantibodies, is associated with thymic hyperplasia characterized by ectopic germinal centers that contain pathogenic antibody-producing B cells. Our thymic transcriptome study demonstrated increased expression of CCL21, a recruiter of immune cells. Accordingly, we are investigating its implication in MG pathogenesis. Methods The expression of CCL21 and its CCR7 receptor was analyzed by enzyme-linked immunosorbent assay and fluorescence-activated cell sorting, respectively. Chemotaxis of T and B cells to CCL21 was measured by transwell assay. The nature of the thymic cells overexpressing CCL21 was investigated by immunochemistry and laser-capture microdissection combined with real-time PCR. Results We demonstrate that CCL21 is overexpressed specifically in hyperplastic MG thymuses, whereas there is no variation in CCR7 levels on blood cells. We show that although CCL21 attracts both human T and B cells, it acts more strongly on naive B cells. CCL21 overexpression is normalized in corticoid-treated MG patients, suggesting that targeting this chemokine could represent a new selective treatment, decreasing the abnormal peripheral lymphocyte recruitment. Moreover, we locate protein and messenger RNA overexpression of CCL21 to specific endothelial vessels. Investigation of the nature of these vessels demonstrated different angiogenic processes in MG thymuses: high endothelial venule angiogenesis and lymphangiogenesis. Unexpectedly, CCL21 overexpression originates from afferent lymphatic endothelial vessels. Interpretation We postulate that thymic overexpression of CCL21 on specialized lymphatic vessels results in abnormal peripheral lymphocyte recruitment, bringing naive B cells in contact with the inflammatory environment characteristic of MG thymuses, where they can be sensitized against AChR. Ann Neurol 2009;66:521,531 [source] Reactive lymphadenopathy in Ugandan patients and its relationship to EBV and HIV infectionAPMIS, Issue 4 2009SAM KALUNGI In Uganda, a large number of biopsied enlarged lymph nodes is diagnosed as reactive lymphoid hyperplasia (RLH) not indicative of a specific etiologic agent. The aim of this study was to examine the spectrum of RLH in lymph node biopsies in Ugandan patients and their possible association with HIV and EBV infection. Ninety biopsies were retrieved and included in the study. The predominant RLH type was follicular, found in 45 (50.0%) of the cases. Positive staining for LMP-1 was found in six cases (6.7%), EBNA-1 in 36 cases (40.0%) and HIV1-p24 in 15 cases (16.7%), respectively. A combination of EBV and HIV positivity was found in 46 (52.2%) of the cases. EBV infection was associated with hyperplastic germinal centers (p<0.01). HIV1-p24 positive staining was associated with follicle fragmentation (p<0.01) but not hyperplastic GC (p=0.08). In conclusion, RLH in Ugandan patients is frequently associated with EBV and HIV infection. The histologic features of the lymph nodes are not specific for any individual infection, but a high number of EBV-positive cases are associated with hyperplastic GC, and follicular fragmentation is characteristic of HIV infection. [source] Follicular lymphoid hyperplasia of the oral cavity representing progressive transformation of germinal center,APMIS, Issue 3 2005Case report Follicular lymphoid hyperplasia (FLH) of the oral cavity is a rare and poorly understood lymphoproliferative disorder. We present a case of FLH of the oral cavity presenting with progressive transformation of germinal center (PTGC). The patient was a 49-year-old Japanese woman presenting with a hard mass in the right cheek. The resected specimen contained numerous lymphoid follicles with active germinal centers and a portion of the lymphoid follicles exhibited PTGC. The PTGCs contained a few large lymphoid cells resembling lymphocytic and histiocytic Reed-Sternberg cells of nodular lymphocyte-predominant Hodgkin lymphoma. The PTGC was surrounded by groups of epithelioid cells. In situ hybridization studies demonstrated strong expression of Epstein-Barr virus (EBV)-encoded small RNA in scattered large lymphoid cells in the PTGC. Although the etiology of FLH of the oral cavity remains unclear, the present case suggests that a subset of FLH of the oral cavity appears to be an EBV-associated lymphoproliferative disorder. [source] Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in elderly patients Report of three casesAPMIS, Issue 12 2003MASARU KOJIMA Three cases of Epstein-Barr virus (EBV)-related lymphoproliferative disorders in elderly patients showing autoimmune disease-associated lymphadenopathy-like clinicopathological findings have been reported. Clinically, they were characterized by systemic lymphadenopathy, "B" symptoms, polyclonal hypergammaglobulinemia, elevated serum LDH and transient presence of various autoantibodies, and absence of atypical lymphocytosis in peripheral blood. One case was associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, they exhibited numerous lymphoid follicles with hyperplastic germinal centers and atypical interfollicular widening with prominent vascular proliferation. In the paracortical area, there was a mixed infiltrate comprising small to medium-sized lymphocytes and plasma cells, and variable numbers of eosinophils and T- and B-immunoblasts. In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center as well as in the interfollicular area. Polymerase chain reaction demonstrated that neither clonal rearrangement of T-cell receptor ,-gene nor immunoglobulin heavy-chain rearrangement was detected in two of the cases examined. Although acute EBV infection rarely occurs in older adults, EBV related to reactive lymphoproliferative disorder should be added to the differential diagnosis of autoimmune disease-associated lymphadenopathy and node-based peripheral T-cell lymphoma in elderly patients. [source] Nodal marginal zone B-ceil lymphoma resembling plasmacytoma arising from a plasma cell variant of localized Castleman's diseaseAPMIS, Issue 7-8 2002a case report Nodal marginal zone B-cell lymphoma (NMZBL) occasionally represents prominent plasma cell differentiation. Recently, primary lymph node plasmacytoma has been suggested to represent an extremely plasmacytic differentiation of NMZBL. We here report a case of NMZBL showing histological features resembling plasmacytoma arising from a plasma cell variant of localized Castleman's disease (PCLCD). The patient was a 69-year-old Japanese female with a 20-year history of a right inguinal mass. Histologically, a prominent proliferation of plasma cells occupied the interfollicular area of the central portion of the lymph node, whereas centrocyte-like (CCL) cells were the main cellular component in the peripheral portion of the lymph node. Although most of the plasma cells were mature ,Marshalko-type', occasional atypical forms with enlarged nuclei were also present. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry study revealed that both plasma cells and some CCL cells had a monotypic intracytoplasmic lambda light chain. When monoclonal plasma cell infiltration is observed in PCLCD, the light chains are mostly restricted to the lambda chain. This case suggests that some plasma cell-containing tumors arising from PCLCD may represent a variant of NMZBL. [source] Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma A clinicopathological study of nine cases,APMIS, Issue 6 2001Masaru Kojima Acute viral lymphadenitis, especially infectious mononucleosis (IM), often shows the presence of Reed-Sternberg-like cells, resulting in confusion with Hodgkin's disease. However, acute viral lymphadenitis requiring differential diagnosis from non-Hodgkin's lymphoma is not widely recognized. We describe the clinicopathological and immunohistochemical features of lymph node lesions from nine such patients which pose serious problems of differential diagnosis from low-grade peripheral T-cell lymphoma. There were three males and six females with ages ranging from 21 to 44 years (median 25 years). All patients had "B" symptoms and multicentric lymphadenopathy. The clinical course was also self-limiting. Each lymph node specimen showed an obvious expansion of an interfollicular area by pleomorphic and polymorphous infiltration with an increased number of arborizing postcapillary venules. The infiltrate was composed of variable numbers of small and medium-sized lymphocytes, immunoblasts, plasma cells in various stage of maturation and occasional granulocytes. The small lymphocytes usually had regular round nuclei, whereas the medium-sized lymphocytes occasionally showed nuclear pleomorphism. Hyperreactivity of B-lymphocytes, including hyperplastic germinal centers and/or foci of monocytoid B-cells, was seen in parts of the lesion. The majority of the interfollicular T-lymphocytes, including T-immunoblasts, expressed CD8 antigen. Various numbers of TIA-1-positive small and medium-sized T-cells were observed in the paracortical area. Despite these findings, the overall histological picture of this series posed serious difficulties when differentially diagnosing this condition from low-grade peripheral T-cell lymphomas such as angioimmunoblastic T-cell (AILD) and T-zone types, indicating that viral lymphadenitis occasionally presents with histological features of AILD and T-zone lymphomas. To avoid overdiagnosis and overtreatment, we emphasize the need to pay careful attention to the clinical and laboratory findings as well as the morphological features. [source] | ||||||||||||||||||||||||||||