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

OPEN The Journal of clinical investigation | 28 Feb 2017

K Rubtsova, AV Rubtsov, JM Thurman, JM Mennona, JW Kappler and P Marrack
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.
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Concepts
Myasthenia gravis, Glomerulonephritis, Sjögren's syndrome, Cell nucleus, Rheumatoid arthritis, Systemic lupus erythematosus, Autoimmune diseases, Lupus erythematosus
MeSH headings
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