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.
[1]Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 200032, Peoples R China.
[2]Univ Tokyo, Inst Med Sci, Int Res & Dev Ctr Mucosal Vaccines, Div Mucosal Barriol, Tokyo 1420054, Japan.
[3]Keio Univ, Fac Pharm, Dept Biochem, Tokyo 1058512, Japan.
[4]Natl Inst Infect Dis, Dept Immunol, Tokyo 1628640, Japan.
[5]RIKEN, Ctr Integrat Med Sci, Lab Immunotherapy, Yokohama, Kanagawa 2300045, Japan.
[6]RIKEN, Ctr Integrat Med Sci, Lab Autoimmune Dis, Yokohama, Kanagawa 2300045, Japan.
[7]Tokyo Med & Dent Univ, Med Res Inst, Dept Immunol, Tokyo 1138510, Japan.
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