T-bet regulates T cell-independent plasmablast responses during intracellular bacterial infection

Abstract

Abstract T-bet+ B cells have emerged as a major B cell subset associated with both protective immunity and autoimmunity. T-bet is considered to be a master transcription factor in type I adaptive immune responses to intracellular pathogens, a response characterized by the production of interferon gamma. Our studies have shown that infection with the intracellular bacterium, E. muris, generates both extrafollicular T cell-independent T-bet+ CD11c+ IgM-secreting plasmablasts (PB), as well as T-bet+ CD11c+ IgM memory cells. Both of these B cell populations play key roles in antigen-specific humoral immunity, although the role of T-bet in their development had not been resolved. Although T-bet is often considered to define lineage in Type I B cells, we found that T-bet was dispensable for memory B cell development. Memory B cells from mice with B cell-specific T-bet deficiency exhibited nearly identical surface marker expression as those of wild-type mice, including CD11c, CD73, PD-L2, CD80, CD38, CD95, and CXCR3. In contrast, T-bet-deficient early CD11c+ splenic PB were significantly reduced in frequency, suggesting that T-bet regulates PB, but not memory cell development or differentiation. As has been reported, antigen-specific IgG2c was no longer the dominant serum antibody isotype in mice lacking B cell T-bet expression. Our data suggest that a critical function of T-bet in B cells is to promote the differentiation of short-lived antibody-secreting PB, and to restrict class switching to protective IgG2c antibodies. Our findings are relevant to how T-bet+ B cells function not only in pathogen-specific immunity, but also in autoimmune diseases, wherein the quality of the humoral response is of critical importance.