scholarly journals BAFF/APRIL Inhibition Decreases Selection of Naive but Not Antigen-Induced Autoreactive B Cells in Murine Systemic Lupus Erythematosus

2011 ◽  
Vol 187 (12) ◽  
pp. 6571-6580 ◽  
Author(s):  
Weiqing Huang ◽  
Ioana Moisini ◽  
Ramalingam Bethunaickan ◽  
Ranjit Sahu ◽  
Meredith Akerman ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Murine Systemic Lupus Erythematosus ◽  
Selection Of

scholarly journals Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients

JCI Insight ◽  
2018 ◽  
Vol 3 (17) ◽  
Author(s):  
Weiqing Huang ◽  
Tam D. Quach ◽  
Cosmin Dascalu ◽  
Zheng Liu ◽  
Tungming Leung ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Negative Selection ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Selection Of

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 MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti–double-stranded DNA B Cells

1999 ◽  
Vol 189 (11) ◽  
pp. 1799-1814 ◽  
Author(s):  
Laura Mandik-Nayak ◽  
Su-jean Seo ◽  
Caroline Sokol ◽  
Kathryn M. Potts ◽  
Anh Bui ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Genetic Background ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Developmental Arrest ◽  
Double Stranded Dna ◽  
Dna Antibodies ◽  
Cell Defect

A hallmark of systemic lupus erythematosus and the MRL murine model for lupus is the presence of anti–double-stranded (ds)DNA antibodies (Abs). To identify the steps leading to the production of these Abs in autoimmune mice, we have compared the phenotype and localization of anti-dsDNA B cells in autoimmune (MRL+/+ and lpr/lpr) mice with that in nonautoimmune (BALB/c) mice. Anti-dsDNA B cells are actively regulated in BALB/c mice as indicated by their developmental arrest and accumulation at the T–B interface of the splenic follicle. In the MRL genetic background, anti-dsDNA B cells are no longer developmentally arrested, suggesting an intrinsic B cell defect conferred by MRL background genes. With intact Fas, they continue to exhibit follicular exclusion; however, in the presence of the lpr/lpr mutation, anti-dsDNA B cells are now present in the follicle. Coincident with the altered localization of anti-dsDNA B cells is a follicular infiltration of CD4 T cells. Together, these data suggest that MRL mice are defective in maintaining the developmental arrest of autoreactive B cells and indicate a role for Fas in restricting entry into the follicle.

scholarly journals Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus

2005 ◽  
Vol 115 (11) ◽  
pp. 3205-3216 ◽  
Author(s):  
Amedeo Cappione ◽  
Jennifer H. Anolik ◽  
Aimee Pugh-Bernard ◽  
Jennifer Barnard ◽  
Paul Dutcher ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Germinal Center ◽  
Human Systemic Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells

scholarly journals Intrinsic B cell defects in NZB and NZW mice contribute to systemic lupus erythematosus in (NZB x NZW)F1 mice.

1996 ◽  
Vol 184 (3) ◽  
pp. 853-861 ◽  
Author(s):  
L Reininger ◽  
T H Winkler ◽  
C P Kalberer ◽  
M Jourdan ◽  
F Melchers ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Lupus Erythematosus ◽  
Fetal Liver ◽  
Systemic Lupus ◽  
Murine Systemic Lupus Erythematosus ◽  
B Lineage

We have previously shown that long-term in vitro proliferating fetal liver pre-B cell lines derived from autoimmune-prone (NZB x NZW)F1 (BW) mice, but not normal (B6 x DBA2)F1 mice, can differentiate in severe combined immunodeficient (SCID) mice to produce elevated levels of serum immunoglobulin (Ig) M and IgG, and high titers of antinuclear antibodies The contribution of parental NZB and NZW strains to B cell abnormalities of BW hybrid mice was investigated here by preparing pre-B cells and transferring them into immunodeficient SCID- and RAG-2-targeted mice. We show that transfer of NZB pre-B cells led to a marked IgM hypergammaglobulinemia and to the production of limited amounts of IgG2a. On the other hand, the transfer of NZW pre-B cell lines led to moderately elevated IgM levels and marked hypergammaglobulinemia of IgG2a. High IgM and low IgG anti-DNA titers are found in the recipients of NZB pre-B cells, whereas those receiving NZW pre-B cells contained lower levels of IgM and high titers of IgG anti-DNA. In marked contrast, essentially identical titers of antibodies directed against a non-self-antigen, DNP, are found in all group of pre-B cell recipients. Thus, B-lineage cells of both NZB and NZW parental strains manifest abnormalities associated with the development of this lupus-like disease. Therefore, the present study strongly suggests a complex inheritance of B cell abnormalities in autoimmune-prone (NZB x NZW)F1 mice and emphasizes the critical importance of intrinsic B cell defects in the development of murine systemic lupus erythematosus.

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 Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosus

2003 ◽  
Vol 48 (2) ◽  
pp. 495-506 ◽  
Author(s):  
Xiaobo Wang ◽  
Weiqing Huang ◽  
Lena E. Schiffer ◽  
Masahiko Mihara ◽  
Alla Akkerman ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Murine Systemic Lupus Erythematosus
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