Stauss Dennis, Brunner Cornelia, Berberich-Siebelt Friederike, Höpken Uta E, Lipp Martin, Müller Gerd
Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Department of Physiological Chemistry, Department of Oto-Rhino-Laryngology Head and Neck Surgery, University of Ulm, Ulm, Germany.
EMBO J. 2016 Apr 15;35(8):881-98. doi: 10.15252/embj.201591459. Epub 2016 Mar 8.
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 thePou2af1gene, 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 theBcl6andBtlapromoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 andBTLA, 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.
滤泡辅助性T(Tfh)细胞是生发中心反应和长期体液免疫的关键调节因子。Tfh细胞分化需要转录抑制因子Bcl6的持续表达;然而,其在CD4(+)T细胞中的调控机制尚未完全明确。在此,我们报道由Pou2af1基因编码的转录共激活因子Bob1可促进Bcl6表达和Tfh细胞发育。我们发现Bob1与八聚体转录因子Oct1/Oct2一起可直接结合并激活Bcl6和BTLA启动子。混合骨髓嵌合体显示,Bob1是正常水平Bcl6和BTLA表达所必需的,从而以T细胞内在方式控制Tfh区室的库大小和组成。我们的数据表明,T细胞表达的Bob1直接参与Tfh细胞分化,并且是产生正常T细胞依赖性B细胞反应所必需的。