B cells expressing the transcription factor T-bet drive lupus-like autoimmunity
Kira Rubtsova, Anatoly V. Rubtsov, Joshua M. Thurman, Johanna M. Mennona, John W. Kappler, Philippa Marrack
Kira Rubtsova, Anatoly V. Rubtsov, Joshua M. Thurman, Johanna M. Mennona, John W. Kappler, Philippa Marrack
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Research Article Autoimmunity Immunology

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

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 7

Mer–/– and Nba2 mice with B cell–specific T-bet deletion exhibit reduced titers of autoantibodies, and reduced frequency of CD11c+ and GC B cells.

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Mer–/– and Nba2 mice with B cell–specific T-bet deletion exhibit reduce...
(A) Titers of anti-chromatin IgG in the serum of Mer–/– and Mer–/– × T-betfl/fl × CD19Cre/WT mice at different ages (as indicated) assessed by ELISA (n = 10 mice per group). (B) Quantification of frequency of T-bet+CD11c+ B cells, GC B cells, and early plasmablasts in 4-month-old Mer–/– × T-betfl/fl × CD19Cre/WT versus Mer–/– mice. Bar graphs represent mean ± SEM (n = 4 mice per group, representative of 3 independent experiments). (C) Titers of anti-chromatin IgG and IgG2a in the serum of Nba2 and Nba2 × T-betfl/fl × CD19Cre/WT mice assessed by ELISA (n = 10 mice per group). *P < 0.05, **P < 0.01, ***P < 0.001 by 1-way ANOVA followed by Newman-Keuls analysis. NS, not significant.