EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity.
EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity.
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EAF2介导生发中心B细胞凋亡以抑制过度免疫反应并预防自身免疫
DOI：
10.1038/ncomms10836
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发表时间：
2016-03-03
影响因子：
16.6
通讯作者：
Wang JY
中科院分区：
文献类型：
--
作者：
Li Y;Takahashi Y;Fujii S;Zhou Y;Hong R;Suzuki A;Tsubata T;Hase K;Wang JY
生发中心（GC） B细胞的调节凋亡对正常的体液免疫应答至关重要。ell相关因子2 （EAF2）调节转录延伸，并已被证明是雄激素响应的潜在肿瘤抑制因子，通过诱导前列腺细胞凋亡。本研究表明，EAF2在不同免疫细胞类型的GC B细胞中选择性上调，并在体外和体内促进GC B细胞凋亡。在t依赖性免疫应答中，EAF2缺乏导致GCs增大和抗体产生升高。在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，突变小鼠会自发产生抗dsdna、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，对维持自身耐受性很重要。EAF2先前被认为是一种转录延伸因子和前列腺癌中缺失的促凋亡基因。作者发现生发中心B细胞的凋亡需要EAF2， EAF2缺陷小鼠会产生过度的抗体反应和自身免疫。
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. EAF2 has been previously known as a transcriptional elongation factor and a proapoptotic gene lost in prostate cancer. Here the authors show that EAF2 is required for apoptosis of germinal centre B cells, and that EAF2-deficient mice develop excessive antibody responses and autoimmunity.