The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

被引:32
|
作者
Stauss, Dennis [1 ]
Brunner, Cornelia [2 ]
Berberich-Siebelt, Friederike [3 ]
Hoepken, Uta E. [1 ]
Lipp, Martin [1 ]
Mueller, Gerd [1 ]
机构
[1] Max Delbruck Ctr Mol Med, Dept Tumor Genet & Immunogenet, Berlin, Germany
[2] Univ Ulm, Dept Physiol Chem, Dept Otorhinolaryngol Head & Neck Surg, D-89069 Ulm, Germany
[3] Univ Wurzburg, Inst Pathol, Josef Schneider Str 2, Wurzburg, Germany
关键词
follicular T helper cells; germinal center; humoral immunity; Pou2af1; T cell differentiation; GERMINAL CENTER FORMATION; NF-KAPPA-B; CXC CHEMOKINE RECEPTOR-5; OCA-B; PEYERS-PATCHES; IMMUNE-RESPONSES; IL-21; PRODUCTION; VIRAL-INFECTION; REPRESSOR BCI6; IGA RESPONSES;
D O I
10.15252/embj.201591459
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4(+) T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses.
引用
收藏
页码:881 / 898
页数:18
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