Details

Autor(en) / Beteiligte

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

Titel

The Transcriptional Repressor Bcl-6 Directs T Follicular Helper Cell Lineage Commitment

Ist Teil von

• Immunity (Cambridge, Mass.), 2009-09, Vol.31 (3), p.457-468

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 RORγt and repressed IFN-γ 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.