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Immunity. 2009 Sep 18;31(3):457-68. doi: 10.1016/j.immuni.2009.07.002. Epub 2009 Jul 23.

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

Author information

1
Immunology and inflammation, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.

Abstract

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.

PMID:
19631565
DOI:
10.1016/j.immuni.2009.07.002
[Indexed for MEDLINE]
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