scholarly journals AB0146 DRUG DEPENDENT ALTERATIONS IN B-CELL REPERTOIRE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH LOW DISEASE ACTIVITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1373.2-1373
Author(s):  
S. Zenz ◽  
B. Dreo ◽  
B. Prietl ◽  
S. Kofler ◽  
H. Sourij ◽  
...  
Keyword(s):  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Repertoire ◽  
Low Disease Activity ◽  
B Cell Repertoire ◽  
Drug Dependent ◽  
B Cell Subsets

Background:B-cells play a major role in the pathogenesis and perpetuation of the immune response in systemic lupus erythematosus (SLE). So far, B-cell subtypes have been studied well, but the precise mechanisms of the B-cell alterations during disease activity and during remission, depending on different medication, are still unclear.Objectives:The aim of our study was to investigate the drug dependent alterations in the B-cell repertoire of SLE patients with low disease activity (SLEDAI – 2K ≤4).Methods:Peripheral blood samples from 39 patients suffering from SLE (mean±SD; age 43±13 years, 87.2% females, disease duration 11.1±7 years) were drawn over 2 years. All SLE patients were in remission or low disease activity (median±SE, SLEDAI of 2.0±1.5). B-cells were characterized using CD19, CD20, CD5, CD27 antibodies and were grouped in naïve (IgD+27-), non-switched memory (IgD+, CD27+), memory (IgD-,CD27+), B1 (CD5+27-) and MBL-like (CD5++) B-cells. A quantitative flow cytometric bead-based assay (QuantiBRITE PE kit from Becton Dickinson) was used for the estimation of CD19 antibodies bound per cell. Further, CD38 and CD86 antibodies were used to characterize the B-cell subsets. All cytometric measurements were performed using a standardized BD LSR Fortessa platform. After 3 years of follow-up, patients’ data about disease activity and current medication were obtained.Results:22 SLE patients were treated with hydroxychloroquine (85.8%) and 19 patients received mycophenolate mofetil (MMF; n=14; 54.6%) or azathioprine (AZA; n= 5; 19.5 %). 5 patients were treated with other DMARDs. Independently of hydroxychloroquine and/or MMF, no significant differences were seen in naïve, non-switched memory, post-switched memory, plasma blasts, B1- or MBL-like B-cells. Patients treated with AZA had significantly lower naïve B-cells (mean±SD, 39.3±6.7vs. 73.1±19.3 %; p = 0.028), but had significantly higher IgD-post switched B-cells (31.2±9.1 vs.12.5 ±9.2 %; p = 0.028, respectively) compared with no AZA-treatment. Interestingly, activated B-cells (5.5±1.5 vs. 1.8±1.1%; p = 0.009) were significantly higher in AZA-treated. After 3 years of follow-up, almost all patients were in remission (median±SE, SLEDAI of 2.0±2.0), except of 3 patients with a SLEDAI of ≥ 6. Interestingly, those patients had at baseline, statistically higher naïve B-cells (p = 0.041) and lower B1-like B-cells (p =0.020) compared with patients with low disease activity.Conclusion:Our results suggest that independently of hydroxychloroquine and/or MMF treatment, all patients with low disease activity had similar normal B-cell subsets. Interestingly, in the small group of patients who were treated with AZA, a reduced regeneration of B-cells was shown. Patients with higher disease and high naïve B-cells showed an increased disease activity after three years.Acknowledgments:The research was performed in “CBmed” and funded by the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien.Disclosure of Interests:None declared

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

scholarly journals Multimodal repertoire analysis unveils B cell biology in health and immune-mediated diseases

2022 ◽  
Author(s):  
Mineto Ota ◽  
Masahiro Nakano ◽  
Yasuo Nagafuchi ◽  
Satomi Kobayashi ◽  
Hiroaki Hatano ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Biology ◽  
Memory B Cells ◽  
Dependent Manner ◽  
Cell Repertoire ◽  
Repertoire Analysis ◽  
Immune Mediated ◽  
B Cell Subsets

Despite involvement of B cells in the pathogenesis of immune-mediated diseases, biological mechanisms underlying their function are scarcely understood. To overcome this gap, comprehensive analysis of the B cell repertoire is essential. Here, we cataloged and investigated the repertoire of five B cell subsets from 595 cases under immune-mediated diseases and health. CDR-H3 length among naive B cells was shortened among autoimmune diseases in an interferon signature-dependent manner. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of systemic lupus erythematosus patients with frequent usage of VDJ genes used mainly in naive B cells and not unswitched-memory B cells of healthy controls. We developed a scoring system for this skewing, and it correlated with peripheral helper T cell transcriptomic signatures and disease activity and decreased after belimumab treatment. Moreover, genetic association analysis identified three molecules possibly involved in somatic hyper-mutation processes in humans. Our multimodal repertoire analysis brings new insights to B cell biology.

scholarly journals A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

2013 ◽  
Vol 210 (9) ◽  
pp. 1665-1674 ◽  
Author(s):  
Anna Vossenkämper ◽  
Paul A. Blair ◽  
Niloufar Safinia ◽  
Louise D. Fraser ◽  
Lisa Das ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Cell Subset ◽  
Cell Repertoire ◽  
Human B Cells ◽  
B Cell Repertoire ◽  
Immature B Cells

We have tracked the fate of immature human B cells at a critical stage in their development when the mature B cell repertoire is shaped. We show that a major subset of bone marrow emigrant immature human B cells, the transitional 2 (T2) B cells, homes to gut-associated lymphoid tissue (GALT) and that most T2 B cells isolated from human GALT are activated. Activation in GALT is a previously unknown potential fate for immature human B cells. The process of maturation from immature transitional B cell through to mature naive B cell includes the removal of autoreactive cells from the developing repertoire, a process which is known to fail in systemic lupus erythematosus (SLE). We observe that immature B cells in SLE are poorly equipped to access the gut and that gut immune compartments are depleted in SLE. Thus, activation of immature B cells in GALT may function as a checkpoint that protects against autoimmunity. In healthy individuals, this pathway may be involved in generating the vast population of IgA plasma cells and also the enigmatic marginal zone B cell subset that is poorly understood in humans.

scholarly journals Clonal analysis of primary B cells responsive to the pathogenic bacterium Salmonella typhimurium.

1987 ◽  
Vol 165 (2) ◽  
pp. 340-358 ◽  
Author(s):  
L W Duran ◽  
E S Metcalf
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lipid A ◽  
Predominant Role ◽  
Cell Repertoire ◽  
Cell Responses ◽  
B Cell Repertoire ◽  
Cell Clones ◽  
B Cell Subsets ◽  
Synthetic Antigens

In the present study, a modification of the splenic focus system is used to analyze the S. typhimurium strain TML (TML)-specific B cell repertoire. The results show that the frequency of primary TML-specific splenic B cells in CBA/Ca mice is approximately 1 per 10(5) B cells and less than 30% of these B cells are specific for LPS. In contrast, the frequency of memory TML-specific cells is approximately 1 per 5-8 X 10(3) splenic B cells and greater than 95% of these B cells are specific for LPS. These results suggest that the frequency of primary TML-specific B cells is extremely low and that it expands 15-20-fold after antigen exposure. It is interesting that less than 30% of the primary B cells are specific for the LPS molecule since it is considered to be the major antigenic determinant on Salmonella organisms. Furthermore, the majority of the LPS-specific anti-TML antibody-producing clones are directed against the LPS O antigen region. Conversely, more than half to two-thirds of the memory LPS-specific anti-TML B cell clones are directed against the KDO or lipid A region of the LPS molecule. These results indicate that the preferential expansion of LPS-specific B cell clones observed after immunization resides primarily in the B cell subsets responsive to the KDO/lipid A moieties on the LPS molecule. Finally, unlike B cell responses to chemically defined antigens, TML stimulates very little IgG1 antibody. IgG2 and IgA isotypes appear to play a predominant role in anti-TML antibody responses, although all H chain classes are produced to some extent. Collectively, these findings are consistent with the responses reported for two other natural antigens, HA and PC. Hence, the pattern of stimulation by infectious agents, such as S. typhimurium, appears to be distinct from that of synthetic antigens. Thus, the studies presented herein have begun to provide insights into those subsets of B cells responsive to S. typhimurium and other infectious disease organisms.

scholarly journals B Cell Abnormalities in Systemic Lupus Erythematosus and Lupus Nephritis—Role in Pathogenesis and Effect of Immunosuppressive Treatments

2019 ◽  
Vol 20 (24) ◽  
pp. 6231 ◽  
Author(s):  
Desmond Y. H. Yap ◽  
Tak Mao Chan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
B Cells ◽  
Lupus Nephritis ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Interaction ◽  
Systemic Lupus ◽  
Cell Repertoire ◽  
B Cell Repertoire

Abnormalities in B cells play pivotal roles in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). Breach in central and peripheral tolerance mechanisms generates autoreactive B cells which contribute to the pathogenesis of SLE and LN. Dysregulation of B cell transcription factors, cytokines and B cell–T cell interaction can result in aberrant B cell maturation and autoantibody production. These immunological abnormalities also lead to perturbations in circulating and infiltrating B cells in SLE and LN patients. Conventional and novel immunosuppressive medications confer differential effects on B cells which have important clinical implications. While cyclophosphamide and mycophenolate mofetil (MMF) showed comparable clinical efficacy in active LN, MMF induction was associated with earlier reduction in circulating plasmablasts and plasma cells. Accumulating evidence suggests that MMF maintenance is associated with lower risk of disease relapse than azathioprine, which may be explained by its more potent and selective suppression of B cell proliferation. Novel therapeutic approaches targeting the B cell repertoire include B cell depletion with monoclonal antibodies binding to cell surface markers, inhibition of B cell cytokines, and modulation of costimulatory signals in B cell–T cell interaction. These biologics, despite showing improvements in serological parameters and proteinuria, did not achieve primary endpoints when used as add-on therapy to standard treatments in active LN patients. Other emerging treatments such as calcineurin inhibitors, mammalian target of rapamycin inhibitors and proteasome inhibitors also show distinct inhibitory effects on the B cell repertoire. Advancement in the knowledge on B cell biology has fueled the development of new therapeutic strategies in SLE and LN. Modification in background treatments, study endpoints and selective recruitment of subjects showing aberrant B cells or its signaling pathways when designing future clinical trials may better elucidate the roles of these novel therapies for SLE and LN patients.

scholarly journals The expansion of activated naive DNA autoreactive B Cells and its association with disease activity in Systemic Lupus Erythematosus patients

2021 ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of Systemic Lupus Erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients' peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis. Thus, aNAV B cells may provide a candidate biomarker for monitoring disease activity in these patients.

scholarly journals Low Numbers of CD27- IgD- 'Double Negative' Senescent B-Cells Early after Reduced Intensity T Cell Depleted Haematopoietic Stem Cell Transplantation Are Predictive of Subsequent Chronic GvHD

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4529-4529
Author(s):  
Francesca Kinsella ◽  
Harriet Protheroe ◽  
Hayden Pearce ◽  
Charlotte F Inman ◽  
Suzy A Eldershaw ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chronic Gvhd ◽  
Subsequent Development ◽  
Haematopoietic Stem Cell ◽  
Cell Repertoire ◽  
Graft Versus Host ◽  
Post Transplant ◽  
B Cell Repertoire ◽  
B Cell Subsets

Chronic graft versus host disease (cGvHD) is an important complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). It is now believed that B cells play a major role in the development of cGvHD as evidenced by the efficacy of B-cell directed therapies, and the disturbances in B cell subsets found in patients. This is characterised by a relative lack of naive B cells and increase in CD27+ (antigen experienced) mature B cells that can mediate host directed responses. Despite this the cellular mechanisms underlying the pathogenesis of cGvHD remain unclear. We investigated the phenotype and function of CD19+ B-cell subsets in a cohort of 46 patients undergoing reduced intensity-conditioned allo-HSCT with alemtuzumab. 76% of patients had myeloid disease and 24% lymphoid disease. All patients received PBMC grafts, fludarabine and melphalan conditioning and 10mg/day alemtuzumab from day -5 for 5 days. Overall survival at 3 years was 65% and relapse free survival was 62%. 16% patients experienced acute GvHD (grade 2+) and 29% developed chronic GvHD. B cell subsets were examined at 6 weeks post-transplant and CD27-IgD- 'double negative' (DN) B-cells were seen to dominate the B cell repertoire (mean 55% of B-cells). DN B-cells are an ill-defined memory B cell subset associated with immune senescence, auto-immune inflammatory conditions and cancer but their role in allo-HSCT has not been described. The frequency of DN B-cells decreased over time, as the naive B cell compartment regenerated, but still represented 31% of B cells at 1 year. However the mean number of DN B cells remained remarkably stable (0.033x109/L at 6 weeks v 0.037x109/L at 1 year). 14% of DN B-cells early post-transplant were transitional (CD24high CD38high) whilst 10% were plasma cells (CD24- CD38high). The remaining 76% had increased CD86 expression compared to memory B-cells (16% v 9.6%; *p=0.039) and lower levels of surface immunoglobulin. DN B-cells were less functional than other B cell subsets with decreased proportions of cells producing IL-2 (20%), IL-6 (17%), IFN-γ (6.2%), and IL-10 (6.2%) compared to naive or memory B cells. They also demonstrated reduced proliferation to in vitro stimulation (Ki-67 5.3%). Importantly, the proportion of DN B cells early post transplant was then studied in relation to transplant outcome and a lower frequency of cells was found to be correlated with subsequent development of cGvHD (38% v 62%; *p=0.04). These data show that senescent CD27-IgD- DN B-cells dominate the B cell repertoire in the early period after lymphocyte-depleted allo-HSCT. Furthermore, they are significantly reduced in patients who subsequently develop cGvHD. These data suggest that early B cell senescence can directly regulate the subsequent development of chronic graft versus host disease and indicate that the composition of the B cell repertoire at an early time-point post-transplant may be used to predict subsequent clinical outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

2019 ◽  
Vol 20 (23) ◽  
pp. 6021 ◽  
Author(s):  
Kongyang Ma ◽  
Wenhan Du ◽  
Xiaohui Wang ◽  
Shiwen Yuan ◽  
Xiaoyan Cai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Therapeutic Interventions ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Regulatory B Cell ◽  
Functional Features ◽  
B Cell Subsets

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have characterized several pathogenic B cell subsets and regulatory B cell subsets involved in the pathogenesis of SLE. Among pathogenic B cell subsets, age-associated B cells (ABCs) are a newly identified subset of autoreactive B cells with T-bet-dependent transcriptional programs and unique functional features in SLE. Accumulation of T-bet+ CD11c+ ABCs has been observed in SLE patients and lupus mouse models. In addition, innate-like B cells with the autoreactive B cell receptor (BCR) expression and long-lived plasma cells with persistent autoantibody production contribute to the development of SLE. Moreover, several regulatory B cell subsets with immune suppressive functions have been identified, while the impaired inhibitory effects of regulatory B cells have been indicated in SLE. Thus, further elucidation on the functional features of B cell subsets will provide new insights in understanding lupus pathogenesis and lead to novel therapeutic interventions in the treatment of SLE.

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