A fundamental function of CD4+ helper (TH) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (TFH) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in TFH cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced TFH-related gene expression and inhibited other TH lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired TFH cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of TFH cell generation.
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