CD11c(+) T-bet(+) B Cells Require IL-21 and IFN-gamma from Type 1 T Follicular Helper Cells and Intrinsic Bcl-6 Expression but Develop Normally in the Absence of T-bet

摘要

CD11c(+) T-bet(+) B cells generated during ehrlichial infection require CD4(+) T cell help and IL-21 signaling for their development, but the exact T cell subset required had not been known. In this study, we show in a mouse model of Ehrlichia muris that type 1 T follicular helper (T-FH1) cells provide help to CD11c(+) T-bet(+) B cells via the dual secretion of IL-21 and IFN-gamma in a CD40/CD40L-dependent manner. T-FH1 cell help was delivered in two phases: IFN-gamma signals were provided early in infection, whereas CD40/CD40L help was provided late in infection. In contrast to T-bet(+) T cells, T-bet(+) B cells did not develop in the absence of B cell-intrinsic Bcl-6 but were generated in the absence of T-bet. T-bet-deficient memory B cells were largely indistinguishable from their wild-type counterparts, although they no longer underwent switching to IgG2c. These data suggest that a primary function of T-bet in B cells during ehrlichial infection is to promote appropriate class switching, not lineage specification. Thus, CD11c(+) memory B cells develop normally without T-bet but require Bcl-6 and specialized help from dual cytokine-producing T-FH1 cells.