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Plasma Cells (plasma + cell)
Kinds of Plasma Cells Terms modified by Plasma Cells Selected AbstractsTranscriptional regulatory cascades controlling plasma cell differentiationIMMUNOLOGICAL REVIEWS, Issue 1 2003Kuo-I Lin Summary:, Plasma cells are the terminally differentiated effector cells of the B lymphocyte lineage. Recently, studies using genetically altered mice and analyses of global gene expression programs have significantly expanded our understanding of the molecular mechanisms regulating plasmacytic differentiation. Specific molecular components of a multistep cascade of transcriptional regulators have been identified. Furthermore, two transcriptional regulators, X box binding protein-1 (XBP-1) and B lymphocyte induced maturation protein-1 (Blimp-1), have been shown to be necessary for plasmacytic differentiation. In addition to providing a mechanistic basis for the induction of genes necessary for immunoglobulin secretion, cessation of cell cycle and other phenotypic changes characteristic of terminally differentiated plasma cells, these studies have led to the important concept that plasmacytic differentiation involves repression of regulators, such as Bcl-6 and Pax5, that are necessary to maintain the earlier developmental phenotype of activated, germinal center B cells. This review describes our current understanding of the transcriptional cascades regulating terminal differentiation of B cells. [source] Cellular characterization of the gouty tophus: A quantitative analysisARTHRITIS & RHEUMATISM, Issue 5 2010Nicola Dalbeth Objective To characterize the cellular architecture of the tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation. Methods Sixteen fixed, paraffin-embedded, uninfected tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the tophus was analyzed by Genmod mixed models analysis. Results Numerous CD68+ mononucleated and multinucleated cells were present within the corona zone. Mast cells were identified in all tophus samples and at similar densities throughout the corona and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma cells were present in very high numbers within the corona zone. The overall number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of cells expressing interleukin-1, (IL-1,) were observed in the corona zone. Transforming growth factor ,1 (TGF,1),expressing mononucleated cells were also identified. The number of CD68+ cells correlated with the number of cells expressing IL-1, (r = 0.691, P = 0.009) and the number expressing TGF,1 (r = 0.518, P = 0.04). Conclusion The tophus represents a complex and organized chronic inflammatory tissue response to monosodium urate monohydrate crystals involving both innate and adaptive immune cells. The coexpression of IL-1, and TGF,1 suggests that both proinflammatory and antiinflammatory factors present within the tophus contribute to a cycle of chronic inflammation, attempted resolution, and tissue remodeling. [source] Myeloma therapy , pursuing the plasma cellEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2009Orhan Sezer No abstract is available for this article. [source] Multiple myeloma , an update on diagnosis and treatmentEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Jo Caers Abstract Multiple myeloma is a plasma cell (PC) malignancy characterized by the accumulation of monoclonal PCs in the bone marrow and the production of large amounts of a monoclonal immunoglobulin or paraprotein. In the past years, new approaches in the diagnosis and treatment were introduced aiming to identify high-risk patients who need proper anti-myeloma treatment. Intensive therapy including autologous hematopoietic stem cell transplantation and the new agents bortezomib, thalidomide, and lenalidomide have improved patients' responses. Further optimalization of the different treatment schedules in well-defined patient groups may prolong their survival. Patient stratification is currently based on patient characteristics, extent of myeloma disease, and associated cytogenetic and laboratory anomalies. More and more gene expression studies are introduced to stratify patients and to individualize therapy. [source] Primary Gougerot,Sjögren syndrome: a dermatological approachJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2006A-M Roguedas Abstract Gougerot,Sjögren syndrome (GSS) is a chronic heterogeneous non-organ-specific autoimmune disease, encompassing a wide spectrum of clinical manifestations. It is characterized by a lymphocytic infiltration of the exocrine glands, also called epitheliitis, resulting in xerostomia and keratoconjunctivitis sicca. The skin can also be involved; for example, xerosis is a consequence of epitheliitis. Dermatological consequences of polyclonal reactivity are vasculitis and manifestations of B-cell proliferation vary from plasma cell infiltrates to B-cell lymphoma. [source] Natural history of unexplained chronic hepatitis after liver transplantationLIVER TRANSPLANTATION, Issue 7 2007Wing-Kin Syn Unexplained chronic hepatitis (CH) in the adult liver allograft recipient is not uncommon, but its natural history and clinical significance is unknown. A retrospective study was undertaken of adult liver allograft recipients to determine the frequency and natural history of unexplained CH. We evaluated only those patients who had undergone ,2 liver biopsies after 6 months and were grafted for indications where recurrent disease could be confidently excluded (alcoholic liver disease [ALD] in those who remained abstinent and fulminant hepatic failure [FHF] from drug reactions). Of 288 patients who were transplanted for ALD or FHF, 30 fulfilled the above criteria. CH was first diagnosed at a median of 15.25 months after transplantation. A total of 24 patients showed mild necroinflammatory changes, and 12 had mild or moderate fibrosis. Liver tests did not reflect the presence or degree of inflammation or fibrosis. After a median of 4 years, necroinflammatory scores were increased in 5; new or progressive fibrosis was noted in 13%; 3 had developed cirrhosis; and 5 developed clinical evidence of portal hypertension. Progressive fibrosis was associated with a high titer of anti-nuclear antibodies (>1:1600) and a portal tract plasma cell infiltrate. There was a trend for correlation between necroinflammatory activity and fibrosis stage, but this did not reach statistical significance (P = 0.06). Serum alkaline phosphatase (P = 0.012) and female gender of the donor (P = 0.033) were associated with progressive fibrosis. Unexplained CH is not uncommon in the liver allograft and may progress to established cirrhosis in a subgroup of patients transplanted for ALD or FHF. Standard liver tests do not reflect the extent of these changes, so protocol liver biopsies may be required to detect these changes. We recommend careful history and follow-up in these patients. Liver Transpl, 2007. © 2007 AASLD. [source] IgG4-related inflammatory aneurysm of the aortic archPATHOLOGY INTERNATIONAL, Issue 4 2009Mitsuaki Ishida IgG4-related sclerosing disease can occur in the cardiovascular system and some inflammatory abdominal aortic aneurysms have been shown to belong to IgG4-related sclerosing disease. Herein is reported a case of IgG4-related inflammatory aortic aneurysm of the aortic arch. A 71-year-old Japanese man was found to have an aneurysm of the aortic arch with maximum dimension of 5.5 cm. The surgically resected aneurysm wall had conspicuous fibrosclerotic changes, dense lymphoplasmacytic infiltration and occasional obliterative phlebitis in the adventitia; the thickness of the adventitia was 6.5 mm. Immunohistochemistry indicated numerous IgG4-positive plasma cell infiltrates; 84% of the IgG-bearing cells were IgG4 positive. The diagnosis of IgG4-related inflammatory aortic aneurysm of the aortic arch was made. Although previously reported IgG4-related inflammatory aortic aneurysms were confined to the abdominal aorta, the present case report demonstrates that IgG4-related inflammatory aortic aneurysm can occur in the aortic arch, thereby extending the spectrum of IgG4-related periaortitis. Further studies are needed to clarify the spectrum of IgG4-related sclerosing disease in the cardiovascular system. [source] Intrathecal pathogenic anti,aquaporin-4 antibodies in early neuromyelitis optica,ANNALS OF NEUROLOGY, Issue 5 2009Jeffrey L. Bennett MD Objective The serum of most neuromyelitis optica (NMO) patients contains autoantibodies (NMO-IgGs) directed against the aquaporin-4 (AQP4) water channel located on astrocyte foot processes in the perivessel and subpial areas of the brain. Our objectives were to determine the source of central nervous system (CNS) NMO-IgGs and their role in disease pathogenesis. Methods Fluorescence-activated cell sorting and single-cell reverse transcriptase polymerase chain reaction were used to identify overrepresented plasma cell immunoglobulin (Ig) sequences in the cerebrospinal fluid (CSF) of an NMO patient after a first clinical attack. Monoclonal recombinant antibodies (rAbs) were generated from the paired heavy and light chain sequences and tested for target specificity and Fc effector function. The effect of CSF rAbs on CNS immunopathology was investigated by delivering single rAbs to rats with experimental autoimmune encephalomyelitis (EAE). Results Repertoire analysis revealed a dynamic, clonally expanded plasma cell population with features of an antigen-targeted response. Using multiple independent assays, 6 of 11 rAbs generated from CSF plasma cell clones specifically bound to AQP4. AQP4-specific rAbs recognized conformational epitopes and mediated both AQP4-directed antibody-dependent cellular cytotoxicity and complement-mediated lysis. When administered to rats with EAE, an AQP4-specific NMO CSF rAb induced NMO immunopathology: perivascular astrocyte depletion, myelinolysis, and complement and Ig deposition. Interpretation Molecular characterization of the CSF plasma cell repertoire in an early NMO patient demonstrates that AQP4-specfic Ig is synthesized intrathecally at disease onset and directly contributes to CNS pathology. AQP4 is now the first confirmed antigenic target in human demyelinating disease. Ann Neurol 2009;66:617,629 [source] IgG4-related systemic disease and lymphoplasmacytic aortitisARTHRITIS & RHEUMATISM, Issue 10 2009John H. Stone We describe herein a patient who developed a dissection of the ascending aorta in the setting of IgG4-related systemic disease, linking IgG4-related systemic disease with a newly-recognized subset of noninfectious aortitis. At the time of aortic surgery, a transmural lymphoplasmacytic infiltrate was detected in the patient's aorta, with a principal focus of inflammation within the media. Immunohistochemical studies demonstrated that >50% of the plasma cells in the lesion stained for IgG4. By in situ hybridization, the plasma cells showed polytypic staining for kappa and lambda light chains, consistent with a polyclonal plasma cell infiltrate. Serologic evaluation revealed that the patient's IgG4 levels were elevated nearly 10-fold. Four years before aortic surgery, the patient had undergone a mediastinal lymph node biopsy. Reexamination of the lymph node revealed features consistent with IgG4-related systemic disease, which had not been recognized at the time of the original biopsy. Glucocorticoid therapy for the IgG4-related systemic disease yielded a prompt response. Recognition that IgG4-related systemic disease can involve the ascending as well as the descending abdominal aorta indicates the need for a change in the way idiopathic aortitis is regarded. This case offers new potential considerations for short- and long-term management of noninfectious aortitis, because of the frequent good response of IgG4-related systemic disease to glucocorticoid treatment without additional therapy. Treatment of the aortitis may prevent progression of the IgG4-related systemic disease to involvement of other organs. IgG4-related systemic disease should be considered in all patients with aortitis judged to be of unknown etiology. [source] Human peripheral blood B-cell compartments: A crossroad in B-cell traffic,CYTOMETRY, Issue S1 2010M. Perez-Andres Abstract A relatively high number of different subsets of B-cells are generated through the differentiation of early B-cell precursors into mature B-lymphocytes in the bone marrow (BM) and antigen-triggered maturation of germinal center B-cells into memory B-lymphocytes and plasmablasts in lymphoid tissues. These B-cell subpopulations, which are produced in the BM and lymphoid tissues, recirculate through peripheral blood (PB), into different tissues including mucosa and the BM, where long-living plasma cells produce antibodies. These circulating PB B-cells can be classified according to their maturation stage into i) immature/transitional, ii) naïve, and iii) memory B-lymphocytes, and iv) plasmablasts/plasma cells. Additionally, unique subsets of memory B-lymphocytes and plasmablasts/plasma cells can be identified based on their differential expression of unique Ig-heavy chain isotypes (e.g.: IgM, IgD, IgG, IgA). In the present paper, we review recent data reported in the literature about the distribution, immunophenotypic and functional characteristics of these cell subpopulations, as well as their distribution in PB according to age and seasonal changes. Additional information is also provided in this regard based on the study of a population-based cohort of 600 healthy adults aged from 20 to 80 years, recruited in the Salamanca area in western Spain. Detailed knowledge of the distribution and traffic of B-cell subsets through PB mirrors the immune status of an individual subject and it may also contribute to a better understanding of B-cell disorders related to B-cell biology and homeostasis, such as monoclonal B-cell lymphocytosis (MBL). © 2010 International Clinical Cytometry Society [source] Multiparameter immunophenotyping by flow cytometry in multiple myeloma: The diagnostic utility of defining ranges of normal antigenic expression in comparison to histology,CYTOMETRY, Issue 4 2010Elisa Cannizzo Abstract Background: Numerous studies have reported on the immunophenotype of plasma cells (PCs) in monoclonal gammopathy of undetermined significance (MGUS) and in plasma cell myeloma (PCM), but very few have examined the immunophenotype of normal PCs. In this study, an objective definition of normal range of expression for each antigen was found on normal control PCs. Using these new ranges of normal expression (new method) is different from using a static 20% of PCs cut-off for all antigens as described in the literature (traditional method). These newly calculated normal ranges for each antigen were applied to our data, and compared to histologic and immunohistochemical findings. Methods: Bone marrow samples from 46 patients with PC neoplasms and 15 normal controls were studied. A minimum of 100 PC were analyzed for each patient and control sample. An 8-color staining method was applied to study the immunophenotype of PCs, using a BD FACSCanto II. Results: By the new ranges of normality calculated in this study it was determined that different antigens have different level of expression on polyclonal PCs. CD19 correlated with histology by both the traditional and new methods, but had superior correlation by the new method. Conclusions: This report is the first 8-color immunophenotypic study of PCM in which a "range of normal expression" for each antigen is defined. This is a critical step to help distinguish between a normal and neoplastic PC immunophenotype and discern which antigens are of diagnostic importance. © 2010 Clinical Cytometry Society [source] Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytologyCYTOPATHOLOGY, Issue 3 2010U. Handa U. Handa, S. Chhabra and H. Mohan Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology Objective:, Plasma cell tumours represent autonomous proliferation of plasma cells and can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, variants of plasma cell myeloma or plasmacytoma. Methods:, We report 12 cases of plasma cell tumours, which were initially diagnosed as plasmacytoma on fine needle aspiration cytology (FNAC). The patients were further subjected to bone marrow examination, serum electrophoresis, urine examination for Bence,Jones proteins, and x-ray examination of the skeleton. Results:, The cytological smears from all cases were cellular and showed numerous plasma cells in varying degrees of maturity. Subsequent to investigations, five cases were labelled as multiple myeloma with secondary extramedullary plasmacytoma, three as solitary bone plasmacytoma and two as primary extramedullary plasmacytoma. In the remaining two cases, bone marrow and urine examination findings were not available, so a conclusive diagnosis of multiple myeloma or solitary plasmacytoma could not be made. Conclusion:, The study highlights the role of FNAC in the diagnosis of plasma cell tumours. Subsequent work-up and follow-up of these patients is important to rule out the presence of multiple myeloma. [source] Fine-needle aspiration cytology of Rosai-Dorfman disease of boneDIAGNOSTIC CYTOPATHOLOGY, Issue 7 2008Xin Jing M.D. Abstract Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a rare, benign self-limiting condition of unknown etiology. Less than a quarter of cases have only extranodal involvement and a few cases of skeletal involvement of Rosai-Dorfman disease without associated lymphadenopathy have been reported in the literature. We herein report cytohistologic findings in a case of sole skeletal Rosai-Dorfman disease in a 51-year-old woman who presented with an expansile, heterogeneous lesion at T11 with cord compression and edema. A CT-guided fine-needle aspiration of T-11 lesion was performed and the sample was processed by ThinPrep technique. The ThinPrep smear showed characteristic features of Rosai-Dorfman disease including hypercellularity with moderate number of histiocytes in a background of lymphocytes, plasma cells, and neutrophils. The histiocytes possessed abundant, pale and vacuolated cytoplasm, rounded nuclei with smooth nuclear membranes, fine chromatin, and distinct nucleoli. The histiocytes showed emperipolesis of lymphocytes and neutrophils. The diagnosis was confirmed by concurrent biopsy with immunhistochemical study. Our case highlighted the role of fine-needle aspiration with ThinPrep technique in the diagnosis of Rosai-Dorfman disease. Diagn. Cytopathol. 2008;36:516,518. © 2008 Wiley-Liss, Inc. [source] MAGNIFYING COLONOSCOPY FOR THE DIAGNOSIS OF INFLAMMATORY CHANGES IN ULCERATIVE COLITISDIGESTIVE ENDOSCOPY, Issue 3 2006Satoshi Sugano Background:, Endoscopic observation is the most effective method for the evaluation of staging in ulcerative colitis (UC). However, in cases with very mild inflammatory activity, histopathological diagnosis may also be required. Unfortunately, biopsy-related accidents are not uncommon. As an alternative, we have used a magnifying colonoscope commonly used for tumor diagnosis to examine in detail the colon mucosa of UC patients in clinical remission, and then compared these findings relative to conventional endoscopy using histopathological diagnosis. Subjects and Methods:, Among UC cases examined by colonoscopy between April 2000 and April 2005, 27 cases without hematochezia for at least 1 month were enrolled in this study. Following observations of inflammatory changes using conventional colonoscopy, magnifying observation and biopsies at a total of 144 sites were evaluated. Using histopathological standards, acute-phase inflammation was indicated by the presence of neutrophil infiltration, whereas chronic-phase inflammation was indicated by infiltration of lymphocytes, plasma cells and eosinophils. Results:, Indicators of significant inflammation by conventional observation was erosion. Under magnification, inflammation appears as superficial defects in mucosa and small whitish spots. When the presence of infiltrating neutrophils was used as a positive histological marker for inflammation, there was no difference in the accuracy of diagnosis by conventional observation (95.1%) versus magnifying observation (97.2%). In contrast, when lymphocyte infiltration was used as a marker, the accuracy of diagnosis increased significantly (88.2%) using magnifying observation relative to conventional observation (61.1%). Conclusions:, Magnifying endoscopy can be used effectively in the evaluation of minute mucosal changes in cases of UC remission. [source] Preclinical development of hybrid cell vaccines for multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007Renata Walewska Abstract Immunotherapy may provide alternative or supplementary treatment of multiple myeloma (MM). We propose that hybrid cells, formed by fusing professional antigen-presenting cells with malignant plasma cells, would induce immune responses capable of mediating tumour regression. The human B-lymphoblastoid cell line, HMy2, was fused in vitro with CD138+ bead-separated myeloma plasma cells from five patients with MM. The hybrid cell lines generated in these studies grew stably in tissue culture, and maintained their phenotypic and functional characteristics, providing self-renewing cell lines with potential for therapeutic vaccination. The hybrid cells stimulated allogeneic and autologous T-cell proliferative responses in vitro to a considerably greater degree than their respective parent myeloma plasma cells, and directly activated both CD4+ and CD8+ T-cell responses. The enhanced T-cell stimulation correlated with expression of CD80 on the hybrid cells, and was inhibited by CTLA4-Ig fusion protein. The hybrid cell lines expressed several tumour-associated antigens known to be expressed in myeloma. These data show that self-replicating cell lines with enhanced immunostimulatory properties and potential for therapeutic vaccination can be generated by in vitro fusion of ex vivo myeloma cells and B-lymphoblastoid cell lines. [source] Arsenic trioxide is effective in the treatment of multiple myeloma in SCID miceEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Philippe Rousselot Abstract: Objectives :,Pharmacological concentrations of arsenic trioxide (ATO) and organic arsenic melarsoprol induce apoptosis in malignant plasma cells. In an attempt to further document the interest of the arsenic in vivo, we treated severe combined immunodeficient (SCID) mice transplanted with human myeloma cells by ATO or melarsoprol. Methods :,Fifty-two SCID mice were irradiated before intraperitoneal (i.p.) injection of plasma cells from five myeloma patients. Engraftment was assessed by serial measurement of the human monoclonal immunoglobulin G (HuMIgG) concentration in mouse serum. Treatment with ATO (10 ,g/g i.p. 5 d a week), melarsoprol (30 ,g/g i.p. 5 d a week) or phosphate buffer saline was started when a sustained growth of the tumor cells was demonstrated. Results :,Seventeen mice developed the human tumor. A significant decrease in HuMIgG amounts was observed in three of five mice of the ATO group, including two that achieved an apparent complete remission persisting up to 5 months after ATO discontinuation. In these mice, no human plasma cells were detected in tissue samples collected postmortem. Soluble human interleukin-6 receptor amount, measured in mice sera as a surrogate marker of the plasma cell proliferation, varied in parallel with HuMIgG concentration. A significant difference in survival was observed between control and ATO treated mice (113 and 158 d, respectively; P = 0.01) whereas no difference could be evidenced in control and melarsoprol groups. Conclusion :,Present study confirms in vivo the in vitro effects of ATO on myeloma cells. Delayed relapses were observed suggesting that prolonged or maintenance therapy has to be considered in future clinical trials. Whether or not this will translate into clinically relevant effect of the drug in myeloma patients deserves further consideration. [source] ALK-positive anaplastic large-cell lymphoma: strong T and B anti-tumour responses may cause hypocellular aspects of lymph nodes mimicking inflammatory lesionsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003B. Borisch Abstract: The anaplastic large cell lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma which occurs in children mostly. The ALK protein is highly immunogenic and elicits both humoral and cellular immune responses. A 15-yr-old child presented with fever and adenopathy and did not respond to antibiotics. Biopsy of the enlarged lymph node contained almost no lymphoid element except for a few CD8-positive T cells, plasma cells and isolated CD30-positive blasts. The patient's condition improved following lymphadenectomy but relapse occurred 3 months later with multiple nodes, high fever and an abdominal mass. This time an ALK-positive ALCL was diagnosed and the retrospective analysis of the initial biopsy revealed rare, isolated ALK+ cells. Molecular analysis showed T-cell clones and oligoclonal B cells in both biopsies and peripheral blood of the patient. The tumour cells harbour a t(2;5) translocation, revealing a null phenotype by immunohistochemistry and no evidence for T-cell clonality by Southern blotting. The patient's serum contained anti-ALK antibodies. Our findings suggest that the T-cell clones and anti-ALK antibodies in this patient constitute an anti-tumour response that caused the hypocellularity of the initial lymph node. Hypocellular and oedematous lymph nodes occurring in a child with evocative symptoms should be tested for the presence of ALK. [source] Signet ring-like light chain myeloma with systemic spreadEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003Joud H. Haidar Abstract: The morphological presentation of malignant plasma cells in multiple myeloma (MM) varies from mature to anaplastic plasma cells with only one reported case of signet ring variant. We describe here another case of signet ring-like lambda light chain MM associated with extra-skeletal spread to lymph nodes, spleen and liver. The clinical and pathological presentations were atypical with no evidence of bone-lytic lesions or monoclonal component on protein electrophoresis, leading to a delay of several years in the diagnosis. Recognition of this morphological entity of MM may help in an early diagnosis of this rare variant. [source] Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2001Lene Meldgaard Knudsen Abstract:Background: Cells belonging to the malignant clone are found in the peripheral blood in myeloma patients. In order to minimise the content of tumour cells in the stem cell product it is crucial to perform stem cell harvest at a time when tumour cells in the peripheral blood are at a minimum. Objective: The aim of the study was to compare the mobilisation kinetics of normal CD34+ cells and myeloma plasma cells during mobilisation with either G-CSF alone or high-dose cyclophosphamide (HDCy) plus G-CSF. Design and methods: Morning blood samples were drawn each day during mobilisation from start of G-CSF or HDCy and to the end of leukapheresis, and were analysed by flow cytometry for content of CD34+ cells and myeloma plasma cells (CD38+ + CD45,). Tumour cells were also estimated by a patient-specific real-time polymerase chain reaction (PCR) method based on the 5, nuclease TaqMan technology. Results: Flow cytometry data from 16 patients showed concomitant mobilisation of CD34+ cells and myeloma plasma cells. Seven patients were mobilised twice; first with G-CSF alone and then with HDCy plus G-CSF. There was no difference between the two mobilisation regimens regarding tumour cell mobilisation kinetics. Real-time PCR was performed in one patient and confirmed the mobilisation of tumour cells at the time when CD34+ blood cells were at a maximum. Conclusions: Tumour cells are mobilised to the peripheral blood at the same time as CD34+ cells in multiple myeloma patients after priming with both G-CSF alone and HDCy in combination with G-CSF. [source] Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2010Rogier Kersseboom Abstract B-cell receptor (BCR)-mediated signals provide the basis for B-cell differentiation in the BM and subsequently into follicular, marginal zone, or B-1 B-cell subsets. We have previously shown that B-cell-specific expression of the constitutive active E41K mutant of the BCR-associated molecule Bruton's tyrosine kinase (Btk) leads to an almost complete deletion of immature B cells in the BM. Here, we report that low-level expression of the E41K or E41K-Y223F Btk mutants was associated with reduced follicular B-cell numbers and significantly increased proportions of B-1 cells in the spleen. Crosses with 3-83,, and VH81X BCR Tg mice showed that constitutive active Btk expression did not change follicular, marginal zone, or B-1 B-cell fate choice, but resulted in selective expansion or survival of B-1 cells. Residual B cells were hyperresponsive and manifested sustained Ca2+ mobilization. They were spontaneously driven into germinal center-independent plasma cell differentiation, as evidenced by increased numbers of IgM+ plasma cells in spleen and BM and significantly elevated serum IgM. Because anti-nucleosome autoantibodies and glomerular IgM deposition were present, we conclude that constitutive Btk activation causes defective B-cell tolerance, emphasizing that Btk signals are essential for appropriate regulation of B-cell activation. [source] Strategies for optimizing targeting and delivery of mucosal HIV vaccinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2009Jeffrey D. Ahlers Abstract Effective frontline defenses against HIV-1 will require targeting vaccines to mucosal tissue in order to induce ,, CD8+ lymphocytes in mucosal effector sites (lamina propria and intraepithelial compartment) as well as antibody secreting plasma cells that can neutralize and limit free virus. A concerted second wave of assault against the virus will require the activation and recruitment of antigen specific memory CD4+ and CD8+ T cells in mesenteric lymph nodes and distal secondary lymphoid organs. New delivery strategies targeting the "right" DC subsets in combination with delivery of mucosal adjuvants and innate signals for activating DC will be essential for mucosal vaccines in order to circumvent the naturally tolerogenic environment and the induction of Tregs. Mucosal delivery of antigen in combination with inflammatory signals has been shown to empower systemic immunization by directing responses to mucosal sites for imprinting optimum mucosal memory. Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines. [source] Organization and maintenance of immunological memory by stroma nichesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2009Koji Tokoyoda Immunological memory is still one of the enigmas of modern immunology. We poorly understand the generation of memory cells from their precursors, the lifestyle of memory cells or their maintenance, reactivation and termination. Here, we discuss the recent evidence suggesting that memory plasma cells, as defined in this review, and memory Th cells are maintained in the bone marrow, resting (in terms of proliferation) in survival niches organized by dedicated stroma cells, which control the homeostasis of immunological memory. [source] Systemic IFN-, drives kidney nephritis in B6.Sle123 miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Anna-Marie Fairhurst Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source] Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin-specific antibodiesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Hans-Christian von Büdingen Abstract Clonally expanded plasma cells (cePC) and their presumed products, oligoclonal immunoglobulin,G bands (OCB), are characteristic findings in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). While cePC and OCB strongly suggest an involvement of B cell-dependent immune mechanisms in the pathogenesis of MS, their actual pathological relevance and target antigens remain unknown. To further understand the potential role played by cePC, we generated a panel of monoclonal antibodies (MS-mAb) from CSF-derived cePC from four patients with early or definite MS. Single-cell RT-PCR of correctly paired heavy and light chain immunoglobulin genes from individual cePC ensured the subsequent resurrection of their original antigen specificity. Immunofluorescence stainings of MS lesion tissue with MS-mAb revealed myelin reactivity in the cePC repertoire of all four patients and intracellular filament reactivity in one patient. While myelin staining by MS-mAb was only rarely detectable in non-MS CNS white matter tissue, it was greatly enhanced at the edge of demyelinating lesions in MS brain tissue. Our findings provide conclusive evidence for the presence of an antigen-driven B cell response in the CSF of MS patients directed against epitopes present in areas of myelin degradation. [source] Glycolipid-activated NKT cells support the induction of persistent plasma cell responses and antibody titersEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008Scott Devera Abstract NKT cell activation with CD1d-binding glycolipid ,-galactosylceramide (,-GC) enhances antibody responses to co-administered T-dependent antigen. The efficacy of ,-GC relative to other CD1d-binding glycolipids and adjuvants is not known. There is little information on how NKT cells affect antibody production beyond initial booster-stimulated recall responses. We therefore tested the hypothesis that ,-GC stimulates induction of plasma cells and antibody responses as effectively as Th1- and Th2-skewing variants of ,-GC and several other adjuvants. C57BL/6 and CD1d,/, mice were immunized with nitrophenol-conjugated keyhole limpet hemocyanin (NP-KLH) plus ,-GC or NP-KLH plus adjuvants before administration of an NP-KLH booster and assessing antibody responses and plasma cell frequency. ,-GC boosted long-term antibody responses as efficiently as all other agents tested and induced plasma cells that were detected in bone marrow 13,weeks after immunization. We then determined whether NKT cells were required in the presence of other adjuvants. CD1d,/, mice had a reduced induction of plasma cells in response to NP-KLH/Alum as compared to C57BL/6 mice. However, NKT cells were not required for the continued presence of those cells that were induced. Although NKT cells are capable of inducing persistent plasma cell responses, they may not play a major role in supporting longevity post-induction. [source] To switch or not to switch , the opposing roles of TACI in terminal B cell differentiationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Ulrich Salzer MD Abstract The TNF superfamily ligands BAFF and APRIL and their three receptors BAFFR, BCMA, and TACI comprise a network that is critically involved in the development and function of humoral immunity. Failure of this complex system is associated with autoimmune disease, B lymphocyte tumours, and antibody deficiency. While BAFF:BAFFR interactions control peripheral B cell survival and homeostasis, BCMA function seems limited to the survival of long-lived bone marrow plasma cells. The functional activity of the third receptor TACI is, however, ambiguous: while TACI,/, mice predominantly develop autoimmunity and lymphoproliferation, TACI deficiency in humans primarily manifests itself as an antibody deficiency syndrome. An article in this issue of the European Journal of Immunology demonstrates a negative regulation via TACI in human B cells by using TACI specific antibodies. B cell proliferation, class switch recombination, and Ig production induced by various stimuli were inhibited via TACI. Within the BAFF/APRIL network, the expression of the receptors and ligands is spatially, as well as temporally, highly regulated at various stages of B cell development and function. Defining the exact contribution of TACI stimulation by specific triggers in vitro enables us to better understand the complex, context-dependent responses initiated by TACI in vivo. See accompanying article http://dx.doi.org/10.1002/eji.200636623 [source] Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challengeEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2006Nathalie Etchart Abstract We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSV-specific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636118 [source] The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2004Patricia Gomez-Bougie Abstract Multiple myeloma is a fatal B,cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that appears to regulate cell survival through the JAK/STAT pathway. In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1. The three major Bim isoforms are expressed in myeloma cells and are negatively regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly associated with Mcl-1 in viable myeloma cells while this interaction is disrupted under apoptosis induction. Of note, while Bim is also found strongly associated to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows Bim to exercise its pro-apoptotic function and to activate Bax. [source] Gastric inflammatory markers and interleukins in patients with functional dyspepsia, with and without Helicobacter pylori infectionFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2005Leif P. Andersen Abstract Helicobacter pylori is the most important cause of gastritis, peptic ulcers and the development of gastric cancer. The chronic active inflammation is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins (IL-8, IL-10 and IFN-,) are involved in the inflammatory process in the gastric mucosa. The aim of this study was to investigate the gastric inflammation in patients with functional dyspepsia. Fifty-three consecutive patients were included and antral biopsies were obtained for histology, culture and immunohistochemistry. The sections were examined for the interleukins IL-4, IL-6, IL-8, IL-10 and IFN-, as well as for the cell markers CD4, CD8, CD14, Cd19, CD25 and CD30. Only CD4 and CD19 were significantly increased in patients with increased gastric inflammation and increased density of H. pylori. However, several of the examined markers (IFN-,, IL-8, IL-10 and CD14) showed a non-significant trend to be increased in patients with extensive gastric inflammation and high density of H. pylori. Therefore, an arbitrary index (IM11) for all the 11 immunological markers was made as an average value for each of the four morphological groups. For the four morphologically different groups of patients the values were 0.49, 0.77, 0.86 and 1.25, respectively. Significant increases in the index from none to moderate antral inflammation as well as the density of H. pylori were found (p < 0.001). By using an index of inflammatory markers trends can be summarized and thereby significant which may be of importance when gastric inflammation is investigated in children and patients with functional dyspepsia. [source] Eosinophilic angiocentric fibrosis of the sinonasal tract: Report on the clinicopathologic features of a case and review of the literature,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2002Emílio M. Pereira MD Abstract Background Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory lesion of the sinonasal tract that occurs mainly in young to middle-aged female patients. Only two previous cases affecting male patients have been reported, and its etiopathogenesis remains unknown. The authors report on the third case of the entity in a male patient and review the 12 previously reported cases. Case Report A 52-year-old male patient was initially seen with a 15 years history of allergic rhinitis, progressive nasal obstruction, and left-sided hearing loss. All laboratory tests were unremarkable, except the nasal discharge eosinophil count that showed a conspicuous eosinophilia. The video-assisted-nasofibroscopic examination and CT scans disclosed a thickened deviated nasal septum with a subjacent infiltrative lesion. The histologic analysis of the nasal septum showed a variable mixed inflammatory cellular infiltration mainly composed of eosinophils, plasma cells, and histiocytes with a perivascular distribution; in other areas, an angiocentric fibrosing lesion with a peculiar perivascular onion-skin pattern was observed. The patient had a partial resection of the lesion with symptomatic control. Conclusions The presence of rhinitis and nasal eosinophilia in our case associated with the clinical aspects of the previously reported cases further support an allergic cause for EAF. © 2002 Wiley Periodicals, Inc. Head Neck 24: 307,311, 2002; DOI 10.1002/hed.10041 [source] | |||||||||||||||||||||||||||||||||||||