Andris Fabienne, Denanglaire Sébastien, Anciaux Maelle, Hercor Mélanie, Hussein Hind, Leo Oberdan
Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Brussels, Belgium.
Front Immunol. 2017 Apr 27;8:480. doi: 10.3389/fimmu.2017.00480. eCollection 2017.
Follicular helper T cells (Tfh) have been identified as the primary cell subpopulation regulating B cell responses in germinal centers, thus supporting high-affinity antibody production. Among the transcription factors orchestrating Tfh cell differentiation and function, the role played by the proto-oncogene c-Maf remains poorly characterized. We report herein that selective loss of c-Maf expression in the T cell compartment results in defective development of Tfh cells in response to both antigen/adjuvant vaccinations and commensal intestinal bacteria. Accordingly, c-Maf expression in T cells was essential for the development and high-affinity antibody secretion in vaccinated animals. c-Maf was expressed early, concomitantly to BCL6, in Tfh cell precursors and found to regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and the regulation of humoral immune responses to T-cell-dependent antigens.
滤泡辅助性T细胞(Tfh)已被确定为调节生发中心B细胞反应的主要细胞亚群,从而支持高亲和力抗体的产生。在协调Tfh细胞分化和功能的转录因子中,原癌基因c-Maf所起的作用仍不清楚。我们在此报告,T细胞区室中c-Maf表达的选择性缺失导致在抗原/佐剂疫苗接种和共生肠道细菌刺激下Tfh细胞发育缺陷。因此,T细胞中c-Maf的表达对于接种疫苗动物的Tfh细胞发育和高亲和力抗体分泌至关重要。c-Maf在Tfh细胞前体中与BCL6同时早期表达,并被发现以细胞自主方式调节Tfh细胞命运。总之,我们的研究结果揭示了c-Maf在Tfh细胞分化和对T细胞依赖性抗原的体液免疫反应调节中的一种新的、非冗余的功能。