Li Yingqian, Takahashi Yoshimasa, Fujii Shin-ichiro, Zhou Yang, Hong Rongjian, Suzuki Akari, Tsubata Takeshi, Hase Koji, Wang Ji-Yang
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 142-0054, Japan.
Nat Commun. 2016 Mar 3;7:10836. doi: 10.1038/ncomms10836.
Regulated apoptosis of germinal centre (GC) B cells is critical for normal humoral immune responses. ELL-associated factor 2 (EAF2) regulates transcription elongation and has been shown to be an androgen-responsive potential tumour suppressor in prostate by inducing apoptosis. Here we show that EAF2 is selectively upregulated in GC B cells among various immune cell types and promotes apoptosis of GC B cells both in vitro and in vivo. EAF2 deficiency results in enlarged GCs and elevated antibody production during a T-dependent immune response. After immunization with type II collagen, mice lacking EAF2 produce high levels of collagen-specific autoantibodies and rapidly develop severe arthritis. Moreover, the mutant mice spontaneously produce anti-dsDNA, rheumatoid factor and anti-nuclear antibodies as they age. These results demonstrate that EAF2-mediated apoptosis in GC B cells limits excessive humoral immune responses and is important for maintaining self-tolerance.
生发中心（GC）B细胞的程序性凋亡对于正常的体液免疫反应至关重要。ELL相关因子2（EAF2）调节转录延伸，并且已被证明通过诱导凋亡在前列腺中是一种雄激素反应性潜在肿瘤抑制因子。在这里，我们表明EAF2在各种免疫细胞类型中的GC B细胞中选择性上调，并在体外和体内促进GC B细胞的凋亡。EAF2缺陷导致在T细胞依赖性免疫反应期间生发中心扩大和抗体产生增加。用II型胶原免疫后，缺乏EAF2的小鼠产生高水平的胶原特异性自身抗体并迅速发展为严重的关节炎。此外，随着年龄的增长，突变小鼠自发产生抗双链DNA、类风湿因子和抗核抗体。这些结果表明，EAF2介导的GC B细胞凋亡限制了过度的体液免疫反应，并且对于维持自身耐受性很重要。
