title: EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity.
abstract: 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.
authors.affiliation: 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.|Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Laboratory for Immunotherapy, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Rongjian
authors.initials: R
authors.lastname: Hong
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
authors.affiliation: 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.|Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Ji-Yang
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015551:Autoimmunity / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010581:Peyer's Patches / Q000166:cytology; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C483108:FESTA protein, mouse; D009687:Nuclear Proteins; D015534:Trans-Activators