Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 9, Pages 3525-3531Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1600017
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Funding
- National Institutes of Health [R01HL075453, R01AI084457, R01AI071163, DP3DK097672, K08AI112993]
- Benaroya Family Gift Fund
- American College of Rheumatology/Rheumatology Research Foundation Rheumatology Scientist Development Award
- Arnold Lee Smith Endowed Professorship for Research Faculty Development
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Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear Abs. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remain unclear. We report that, although surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACI(+) transitional cells from BAFF-transgenic mice are characterized by an activated, cycling phenotype, and the TACI(+) cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase and T-bet, and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells from BAFF-transgenic mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism through which BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells.
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