The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment
Follicular helper T (Tfh) cells provide selection signals to germinal center B cells, which is essential for long-lived antibody responses. High CXCR5 and low CCR7 expression facilitates their homing to B cell follicles and distinguishes them from T helper 1 (Th1), Th2, and Th17 cells. Here, we showed that Bcl-6 directs Tfh cell differentiation: Bcl-6-deficient T cells failed to develop into Tfh cells and could not sustain germinal center responses, whereas forced expression of Bcl-6 in CD4(+) T cells promoted expression of the hallmark Tfh cell molecules CXCR5, CXCR4, and PD-1. Bcl-6 bound to the promoters of the Th1 and Th17 cell transcriptional regulators T-bet and RORgammat and repressed IFN-gamma and IL-17 production. Bcl-6 also repressed expression of many microRNAs (miRNAs) predicted to control the Tfh cell signature, including miR-17-92, which repressed CXCR5 expression. Thus, Bcl-6 positively directs Tfh cell differentiation, through combined repression of miRNAs and transcription factors.
|Authors||Yu, D.; Rao, S.; Tsai, L. M.; Lee, S. K.; He, Y.; Sutcliffe, E. L.; Srivastava, M.; Linterman, M.; Zheng, L.; Simpson, N.; Ellyard, J. I.; Parish, I. A.; Ma, C. S.; Li, Q. J.; Parish, C. R.; Mackay, C. R.; Vinuesa, C. G.;|
|Published Date||2009-01-01 00:00:00|