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Publication : CD11c<sup>+</sup> T-bet<sup>+</sup> B Cells Require IL-21 and IFN-γ from Type 1 T Follicular Helper Cells and Intrinsic Bcl-6 Expression but Develop Normally in the Absence of T-bet.

First Author  Levack RC Year  2020
Journal  J Immunol Volume  205
Issue  4 Pages  1050-1058
PubMed ID  32680956 Mgi Jnum  J:300680
Mgi Id  MGI:6502380 Doi  10.4049/jimmunol.2000206
Citation  Levack RC, et al. (2020) 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. J Immunol 205(4):1050-1058
abstractText  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 (TFH1) 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. TFH1 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 TFH1 cells.
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