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Memory B Cells (memory + b_cell)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Immunology	52%
Hematology	10%

Selected Abstracts

Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4+ T-cell proliferation and IFN-, production in response to myelin basic protein and myelin oligodendrocyte glycoprotein

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2010
Christopher T. Harp
Abstract Recent evidence suggests that B- and T-cell interactions may be paramount in relapsing-remitting MS (RRMS) disease pathogenesis. We hypothesized that memory B-cell pools from RRMS patients may specifically harbor a subset of potent neuro-APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and lymphotoxin-, secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4+ T-cell proliferation and IFN-, secretion in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Notwithstanding the fact that the phenotypic parameters that promote efficient Ag presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4+ T-cell proliferation in response to myelin basic protein and myelin oligodendrocyte glycoprotein was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can activate T cells. [source]

Correction: Memory B cells: Effectors of long-lived immune responses

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010
Stuart G. Tangye
No abstract is available for this article. [source]

Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4+ T-cell proliferation and IFN-, production in response to myelin basic protein and myelin oligodendrocyte glycoprotein

TLR9 stimulation drives naïve B cells to proliferate and to attain enhanced antigen presenting function

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007
Wei Jiang
Abstract Mechanisms that regulate naïve B cell proliferation and function are incompletely defined. In this study, we test the hypothesis that naïve B cell expansion, survival and ability to present antigen to T,lymphocytes can be directly modulated by Toll-like receptor (TLR) agonists. In the absence of B cell receptor stimulation, CpG oligonucleotide, a TLR9 agonist, was particularly efficient in inducing naïve B cell proliferation and survival. Although the expanded naïve B cells did not mature into CD27+ or IgG+ memory B cells, these cells did differentiate into IgM-secreting cells with increased surface expression of HLA-DR, CD40 and CD80. This was associated with an increased potential for these B cells to activate allogeneic T cells. We propose that the activation and expansion of naïve B cells induced by TLR9 agonists could enhance the potential of these cells to interact with cognate antigens and facilitate cell-mediated immune responses. [source]

The germinal center response is impaired in the absence of T cell-expressed CXCR5

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007
Carrie
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]

Intrinsic properties of human and murine memory B cells

IMMUNOLOGICAL REVIEWS, Issue 1 2006
Shannon M. Anderson
Summary:, The central question of how the immune system responds in a qualitatively and quantitatively better way upon re-exposure to a pathogen is largely unanswered. Both the increased frequency of antigen-specific memory cells and the intrinsic properties that memory cells acquire after antigen experience could contribute to the faster and more robust responses seen after repeated exposure to antigen. In the case of the memory B-cell response, it has been difficult to discern the individual contributions of these two effects. However, because of recent advances in identifying memory B cells, there is an increasing understanding of the intrinsic properties of these cells. The current insights into the unique properties of memory B cells and the progress that has been made in understanding how these affect secondary responses in both the human and the mouse systems are discussed. In addition, we compare the various advantages and disadvantages inherent in each of these systems, in terms of studying the intrinsic properties of memory B cells, and introduce the details of the system that we have developed using conventional heavy chain transgenic (Tgic) mice, which addresses some of the drawbacks of traditional memory models. [source]

B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation

LIVER TRANSPLANTATION, Issue 4 2007
Hiroto Egawa
Although the effectiveness of rituximab has been reported in ABO blood group (ABO)-incompatible (ABO-I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO-I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B-cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO-I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B-cell study of the spleen, another 4 patients undergoing ABO-I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABO-compatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti-donor blood-type antibody titer was lower, and clinical and pathological antibody-mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody-mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO-I LDLT patients. Liver Transpl 13:579,588, 2007. © 2007 AASLD. [source]

Sequence and expression analyses of , and , transcripts in patients with waldenström's macroglobulinemia

AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2001
Satoshi Shiokawa
Abstract Waldenström's macroglobulinemia (WM) is a malignant lymphoplasmo-proliferative disorder with monoclonal pentameric immunoglobulin (Ig)M production. The most consistent feature of clonal B cells in the bone marrow (BM) and/or lymph nodes of patients with WM is the presence of pleomorphic B-lineage cells at different stages of maturation, such as small lymphocytes, lymphoplasmacytoid cells, and plasma cells. Monoclonal lymphocytes express , chains with or without , chains. A recent DNA analysis of WM tumor clones showed WM to be derived from B cells that have been selected by antigen at a relatively late stage of differentiation. To further clarify the origin of WM tumor cells, we analyzed the variable (V) domain sequences of tumor derived , and , transcripts. The expression of , transcripts was also examined in peripheral blood (PB) and BM using the reverse transcriptase polymerase chain reaction (RT-PCR) combined with a single-strand conformation polymorphism (SSCP) analysis. The sequences were identical among the , and , transcripts in each patient and the level of somatic mutation in the VH regions expressed by tumor cells was in the same range as that of IgM-only B cells and IgM+IgD+ memory B cells. In our previous RT-PCR-SSCP analysis, a single dominant band of the , isotype was observed in BM and PB in all patients. However, common dominant bands in BM and PB were detected in only one patient in a , transcript analysis. In the rest of the patients, monoclonal , transcripts were only detected in BM. Our results suggest that a normal counterpart of WM cells is somatically mutated IgM+IgD+ and/or IgM-only B cells and the expression patterns of monoclonal , and , transcripts differ between BM and PB in some cases of WM. Am. J. Hematol. 68:139,143, 2001. © 2001 Wiley-Liss, Inc. [source]

Effect of long-term belimumab treatment on b cells in systemic lupus erythematosus: Extension of a phase II, double-blind, placebo-controlled, dose-ranging study,

ARTHRITIS & RHEUMATISM, Issue 1 2010
Annett M. Jacobi
Objective To understand the effects of long-term BLyS inhibition in human systemic lupus erythematosus (SLE). Methods Seventeen patients with SLE who were enrolled in a clinical trial of belimumab, a BLyS-specific inhibitor, plus standard of care therapy were studied. Phenotypic analysis of lymphocytes was performed using flow cytometry. Circulating antibody-secreting cells were enumerated using enzyme-linked immunospot assay. Serum was analyzed by enzyme-linked immunosorbent assay using an antibody that recognizes products of the VH4,34 gene. Lymphocyte counts, Ig levels, and anti,double-stranded DNA antibody levels were available as part of the clinical trial analyses. Results Samples were collected on days 0, 84, 168, 365, and 532 and after day 730. The total number of B cells started to decrease from baseline between days 84 and 168. This was due to a decrease in naive and transitional B cells. CD27+IgD+ memory B cells and plasmablasts decreased only after 532 days, whereas CD27+IgD, memory B cells were not affected, and there were no changes in T cells. Serum IgM levels began to decline between days 84 and 168, but there were no changes in serum levels of IgG, IgG anti-DNA antibodies, or VH4,34 antibodies during the study. SLE patients had more IgM-, IgG-, and autoantibody-producing B cells than did normal controls on day 0. There was only a modest decrease in the frequency of total IgM-producing, but not IgG-producing, cells on days 365 and 532, consistent with the phenotypic and serologic data. Conclusion Our data confirm the dependence of newly formed B cells on BLyS for survival in humans. In contrast, memory B cells and plasma cells are less susceptible to selective BLyS inhibition. [source]

Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

ARTHRITIS & RHEUMATISM, Issue 8 2009
Khalid Muhammad
Objective Transient B cell depletion by rituximab has been used with clinical efficacy in the treatment of patients with rheumatoid arthritis (RA). Previous studies of B cell repopulation have shown long-term numerical reduction in memory B cells. Non,class-switched IgD+CD27+ memory B cells, in particular, repopulate slowly. This study was undertaken to determine whether mutational acquisition in individual B cell receptors in repopulating class-switched and non,class-switched memory B cells is affected by rituximab. Methods Cells obtained from 16 RA patients, 4 healthy donors, and 3 patients who underwent allogeneic stem cell transplantation (ASCT) were analyzed using single B cell sorting followed by nested polymerase chain reaction and Ig VH3 sequencing. Results There was a delayed acquisition of mutations in Ig receptors of IgD+ memory B cells over a period of 6 years after a single course of rituximab. One year after rituximab treatment, 84% of single repopulating IgD+CD27+ B cells were unmutated, and no highly mutated Ig receptors were found (compared with 52% before therapy). Over time, increasing numbers of mutations were detected. Even 6 years after rituximab treatment, however, mutations in IgD+ memory B cells were still significantly reduced. In contrast, class-switched memory B cells repopulated with quantitatively normal mutations. In comparison, in patients undergoing ASCT, IgD+ memory cells repopulated earlier with higher mutations in Ig receptors. Conclusion Our data suggest that IgD+ memory B cells are particularly susceptible to the effects of rituximab, with delayed acquisition of mutations in their Ig receptors still evident 6 years after a single course of rituximab. Our findings indicate that these cells have different requirements for mutational acquisition compared with class-switched memory B cells. [source]

Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy

ARTHRITIS & RHEUMATISM, Issue 9 2007
Jennifer 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]

Gene expression of anti- and pro-apoptotic proteins in malignant and normal plasma cells

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2009
Michel Jourdan
Summary The survival of malignant plasma cells is a key event in disease occurrence, progression and chemoresistance. Using DNA-microarrays, we analysed the expression of genes coding for 58 proteins linked with extrinsic and intrinsic apoptotic pathways, caspases and inhibitor of apoptosis proteins. We considered six memory B cells (MBC), seven plasmablasts (PPC), seven bone marrow plasma cells (BMPC) and purified myeloma cells (MMC) from 92 newly-diagnosed patients. Forty out of the 58 probe sets enabled the separation of MBC, PPC and BMPC in three homogeneous clusters, characterized by an elevated expression of TNFRSF10A, TNFRSF10B, BCL2A1, CASP8, CASP9 and PMAIP1 genes for MBC, of FAS, FADD, AIFM1, BIRC5, CASP CASP2, CASP3 and CASP6 for PPC and of BCL2, MCL1, BID, BIRC3 and XIAP for BMPC. Thus, B cell differentiation was associated with change of expression of pro-apoptotic and anti-apoptotic genes. Regarding MMC, the major finding was TRAIL upregulation that might be counteracted by a high osteoprotegerin production by BM stromal cells and a decreased expression of FAS, APAF1 and BNIP3 compared to normal BMPC. Out of the 40 genes, CASP2 and BIRC5 expression in MMC had adverse prognosis in two independent series of previously-untreated patients. [source]

BAFF: a local and systemic target in autoimmune diseases

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2009
I. Moisini
Summary BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory sites in which there is lymphoid neogenesis. BAFF antagonism has been used in several autoimmune disease models, resulting in B cell depletion, decreased activation of T cells and dendritic cells (DC) and a reduction in the overall inflammatory burden. BAFF, through its interaction with BAFF-R, is required for survival of late transitional, marginal zone and mature naive B cells, all of which are depleted by BAFF blockade. Through their interactions with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation protein), BAFF and its homologue APRIL (a proliferation-inducing ligand), support the survival of at least some subsets of plasma cells; blockade of both cytokines results in a decrease in serum levels of immunoglobulin (Ig)G. In contrast, neither BAFF nor APRIL is required for the survival or reactivation of memory B cells or B1 cells. BAFF also helps DC maturation and interleukin (IL)-6 release and is required for proper formation of a follicular dendritic cell (FDC) network within germinal centres, although not for B cell affinity maturation. The clinical efficacy of BAFF blockade in animal models of autoimmunity may be caused both by the decline in the number of inflammatory cells and by the inhibition of DC maturation within target organs. Blockade of BAFF and its homologue APRIL are being explored for human use; several Phase I and II clinical trials of BAFF inhibitors for autoimmunity have been completed and Phase III trials are in progress. [source]

Measurement of peripheral B cell subpopulations in common variable immunodeficiency (CVID) using a whole blood method

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
B. L. Ferry
Summary Recent reports have described reduced populations of CD27+ memory B cells and increased percentages of undifferentiated B cells in peripheral blood of patients with common variable immunodeficiency (CVID). This work has prompted two attempts to classify CVID based on rapid flow cytometric quantification of peripheral blood memory B cells and immature B cells. Evidence to support the hypothesis that such in vitro B cell classification systems correlate with clinical subtypes of CVID is being sought. For the classification to be useful in routine diagnosis, it is important that the flow cytometric method can be used without prior separation of peripheral blood mononuclear cells (PBMC). We have examined 23 CVID patients and 24 controls, using both PBMC and whole blood, and find an excellent correlation between these methods. The reproducibility of the method was excellent. We classified the CVID patients by all three of the existing classifications, including secretion of immunoglobulin by B cells in vitro as described by Bryant, as well as the more recent flow cytometric classification methods. Only one patient changed classification as a result of using whole blood. [source]