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 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 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 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 The effect of anti-CD40 ligand antibody on B cells in human systemic lupus erythematosus

2002 ◽  
Vol 46 (6) ◽  
pp. 1554-1562 ◽  
Author(s):  
Weiqing Huang ◽  
Jayashree Sinha ◽  
Jeffrey Newman ◽  
Bhoompally Reddy ◽  
Lalbachan Budhai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Cd40 Ligand ◽  
Human Systemic Lupus Erythematosus ◽  
Systemic Lupus

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 Increased Frequency of Pre-germinal Center B Cells and Plasma Cell Precursors in the Blood of Children with Systemic Lupus Erythematosus

2001 ◽  
Vol 167 (4) ◽  
pp. 2361-2369 ◽  
Author(s):  
Edsel Arce ◽  
Deborah G. Jackson ◽  
Michelle A. Gill ◽  
Lynda B. Bennett ◽  
Jacques Banchereau ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Plasma Cell ◽  
Lupus Erythematosus ◽  
Germinal Center ◽  
Systemic Lupus ◽  
Germinal Center B Cells

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
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