The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment.

Immunology and inflammation, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.

Immunity 2009 Sep 18

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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.

Citation

Di Yu, Sudha Rao, Louis M Tsai, Sau K Lee, Yiqing He, Elissa L Sutcliffe, Monika Srivastava, Michelle Linterman, Lei Zheng, Nicholas Simpson, Julia I Ellyard, Ian A Parish, Cindy S Ma, Qi-Jing Li, Christopher R Parish, Charles R Mackay, Carola G Vinuesa. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity. 2009 Sep 18;31(3):457-68