The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation

被引：116

作者：

Carotta, Sebastian ^{[1
,2
]}

Willis, Simon N. ^{[1
,2
]}

Hasbold, Jhagvaral ^{[1
,2
]}

Inouye, Michael ^{[1
,3
,4
]}

Pang, Swee Heng Milon ^{[1
,2
]}

Emslie, Dianne ^{[1
]}

Light, Amanda ^{[1
]}

Chopin, Michael ^{[1
,2
]}

Shi, Wei ^{[1
,5
]}

Wang, Hongsheng ^{[6
]}

Morse, Herbert C., III ^{[6
]}

Tarlinton, David M. ^{[1
,2
]}

Corcoran, Lynn M. ^{[1
,2
]}

Hodgkin, Philip D. ^{[1
,2
]}

Nutt, Stephen L. ^{[1
,2
]}

机构：

[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[3] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia

[4] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia

[5] Univ Melbourne, Dept Comp & Informat Syst, Parkville, Vic 3010, Australia

[6] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 11期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 澳大利亚研究理事会;

关键词：

GERMINAL CENTER B; GENE-EXPRESSION; MATURE B; SPI-B; BLIMP-1; NETWORK; PROGRAM; INFLAMMATION; REPRESSION; GENERATION;

D O I：

10.1084/jem.20140425

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell-promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1-IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation.

引用

页码：2169 / 2181

页数：13

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