A Intronic Element Regulates T Follicular Helper Cell Differentiation.

In response to an intracellular infectious agent, the immune system produces a specific cellular response as well as a T cell-dependent Ab response. Precursor T cells differentiate into effector T cells, including Th1 cells, and T follicular helper (T) cells. The latter cooperate with B cells to form germinal centers and induce the formation of Ab-forming plasmacytes. One major focal point for control of T cell differentiation is the transcription factor BCL6. In this study, we demonstrated that the gene is regulated by FOXO1-binding, -acting sequences located in a highly conserved region of the first intron. In both mouse and human T cells, deletion of the tandem FOXO1 binding sites increased the expression of BCL6 and enhanced the proportion of T cells. These results reveal a fundamental control point for cellular versus humoral immunity.