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B cells expressing the transcription factor T-bet drive lupus-like autoimmunity
Kira Rubtsova, … , John W. Kappler, Philippa Marrack
Kira Rubtsova, … , John W. Kappler, Philippa Marrack
Published February 27, 2017
Citation Information: J Clin Invest. 2017;127(4):1392-1404. https://doi.org/10.1172/JCI91250.
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Research Article Autoimmunity Immunology

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

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Abstract

B cells contribute to multiple aspects of autoimmune disorders and may play a role in triggering disease. Thus, targeting B cells may be a promising strategy for treating autoimmune disorders. Better understanding of the B cell subsets that are responsible for the development of autoimmunity will be critical for developing efficient therapies. Here we have reported that B cells expressing the transcription factor T-bet promote the rapid appearance of autoantibodies and germinal centers in spontaneous murine models of systemic lupus erythematosus (SLE). Conditional deletion of T-bet from B cells impaired the formation of germinal centers and mitigated the development of kidney damage and rapid mortality in SLE mice. B cell–specific deletion of T-bet was also associated with lower activation of both B cells and T cells. Taken together, our results suggest that targeting T-bet–expressing B cells may be a potential target for therapy for autoimmune diseases.

Authors

Kira Rubtsova, Anatoly V. Rubtsov, Joshua M. Thurman, Johanna M. Mennona, John W. Kappler, Philippa Marrack

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Figure 4

Reduced appearance of CD11c+ ABCs, GC B cells, and early plasmablasts in SLE mice with B cell–specific T-bet deletion.

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Reduced appearance of CD11c+ ABCs, GC B cells, and early plasmablasts in...
Representative FACS plots and quantification of the frequency of (A) CD11c+ B cells, (B) GC B cells, and (C) early plasmablasts in the spleens of 4-month-old C57BL/6 (white bars), SLE × T-betfl/fl × CD19Cre/WT (red bars), and SLE × T-betfl/fl × CD19WT/WT (black bars) mice. B cells were gated as live, B220+CD19+CD4–CD8–. Bar graphs represent mean ± SEM (n = 4 mice per group, representative of 3 independent experiments). *P < 0.05, **P < 0.01, ***P < 0.001 by 1-way ANOVA followed by Newman-Keuls analysis. NS, not significant.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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