Role and Regulation of CD11chi T-bet+ B cells in SLE

We examined a large cohort of systemic lupus erythematosus (SLE) patients and found an unusual B cell subset highly expanded. These B cells displayed a unique phenotype and expressed antigens not present on other B cell populations, including high densities of CD11c, FcRL5, and the T-box transcription factor, T-bet, but unexpectedly, were CD40 lo and CD24 − . Although these CD11c hi cells were largely negative for the memory B cell antigen CD27, their telomere length was consistent with memory, rather than naive B cells. Notably, the increase of CD11c hi B cells in SLE significantly correlated with disease severity scores as well as with other markers of disease activity including serum IL-21. While memory B cells characteristically express low densities of IL-21R, these memory CD11c hi B cells were IL-21R bright. In culture, IL-21 was a potent driver of CD11c expression when B cells were co-stimulated through the B cell receptor and CD40. Lastly, CD11c hi B cells in SLE significantly correlated with blood plasma cells as well as a distinct set of autoantibodies, and importantly, were efficiently driven to differentiate into plasma cells in response to activated T cells. These data indicate that among the many roles of IL-21 in regard to B cell activation and differentiation, this pleiotropic cytokine also regulates CD11c hi B cells, and presumably contributes to autoimmunity through the differentiation of autoreactive CD11c hi B cells in SLE.