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

Di Yu, Sudha Rao, Louis M Tsai, Sau K Lee, Yiqing He, Elissa L Sutcliffe, Mnika Srivastava, Michelle Linterman, Lei Zheng, Nicholas Simpson, Julia I Ellyard, Ian A Parish, Cindy S Ma, Qi-Jing Li, Christopher R Parish, Charles Reay Mackay, Carola G Vinuesa

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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.
Original languageEnglish
Pages (from-to)457 - 468
Number of pages12
JournalImmunity
Volume31
Issue number3
DOIs
Publication statusPublished - 2009

Cite this

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. (2009). The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity, 31(3), 457 - 468. https://doi.org/10.1016/j.immuni.2009.07.002