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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yu, D; Rao, S; Tsai, LM; Lee, SK; He, Y; Sutcliffe, EL; Srivastava, M; Linterman, M; Zheng, L; Simpson, N; Ellyard, JI; Parish, IA; Ma, CS; Li, Q-J; Parish, CR; Mackay, CR; Vinuesa, CG

Published Date

  • September 18, 2009

Published In

Volume / Issue

  • 31 / 3

Start / End Page

  • 457 - 468

PubMed ID

  • 19631565

Pubmed Central ID

  • 19631565

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2009.07.002

Language

  • eng

Conference Location

  • United States