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

被引：1026

作者：

Yu, Di ^{[1
,2
]}

Rao, Sudha ^{[2
]}

Tsai, Louis M. ^{[1
]}

Lee, Sau K. ^{[2
]}

He, Yiqing ^{[2
]}

Sutcliffe, Elissa L. ^{[2
]}

Srivastava, Monika ^{[2
]}

Linterman, Michelle ^{[2
]}

Zheng, Lei ^{[1
]}

Simpson, Nicholas ^{[2
]}

Ellyard, Julia I. ^{[2
]}

Parish, Ian A. ^{[2
]}

Ma, Cindy S. ^{[1
]}

Li, Qi-Jing ^{[3
]}

Parish, Christopher R. ^{[2
]}

Mackay, Charles R. ^{[1
,4
,5
,6
]}

Vinuesa, Carola G. ^{[2
]}

机构：

[1] Garvan Inst Med Res, Sydney, NSW 2010, Australia

[2] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia

[3] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA

[4] UNSW, St Vincents Clin Sch, Fac Med, Darlinghurst, NSW 2010, Australia

[5] Monash Univ, Fac Med, Nursing Serv, Clayton, Vic 3800, Australia

[6] Monash Univ, Hlth Serv, Clayton, Vic 3800, Australia

来源：

IMMUNITY | 2009年 / 31卷 / 03期

基金：

英国医学研究理事会;

关键词：

GERMINAL-CENTER FORMATION; CXC CHEMOKINE RECEPTOR-5; CENTER B-CELLS; IMMUNOGLOBULIN PRODUCTION; SYSTEMIC AUTOIMMUNITY; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; GENE-EXPRESSION; C-MAF; DIFFERENTIATION;

D O I：

10.1016/j.immuni.2009.07.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 ROR gamma t 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.

引用

页码：457 / 468

页数：12

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