EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity

Yingqian Li; Yoshimasa Takahashi; Shin Ichiro Fujii; Yang Zhou; Rongjian Hong; Akari Suzuki; Takeshi Tsubata; Koji Hase; Ji Yang Wang

doi:10.1038/ncomms10836

EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity

Yingqian Li, Yoshimasa Takahashi, Shin Ichiro Fujii, Yang Zhou, Rongjian Hong, Akari Suzuki, Takeshi Tsubata, Koji Hase, Ji Yang Wang

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

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.

Original language	English
Article number	10836
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10836
Publication status	Published - 2016 Mar 3

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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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.",

author = "Yingqian Li and Yoshimasa Takahashi and Fujii, {Shin Ichiro} and Yang Zhou and Rongjian Hong and Akari Suzuki and Takeshi Tsubata and Koji Hase and Wang, {Ji Yang}",

note = "Funding Information: We wish to thank Profs Takeshi Tokuhisa, Hiroshi Ohno, Sidonia Fagarasan and Peter Burrows for helpful advice, and Akiko Ukai and Hiromi Mori for technical assistance. This work was in part supported by the National Basic Research Program of China (2015CB943300 to J.Y.W.), the National Natural Science Foundation of China (81373129 and 81571529 to J.Y.W.), and a grant-in-aid for scientific research (C) from Japan Society for the Promotion of Science (25460604 to J.Y.W.).",

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doi = "10.1038/ncomms10836",

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T1 - EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity

AU - Li, Yingqian

AU - Takahashi, Yoshimasa

AU - Fujii, Shin Ichiro

AU - Zhou, Yang

AU - Hong, Rongjian

AU - Suzuki, Akari

AU - Tsubata, Takeshi

AU - Hase, Koji

AU - Wang, Ji Yang

N1 - Funding Information: We wish to thank Profs Takeshi Tokuhisa, Hiroshi Ohno, Sidonia Fagarasan and Peter Burrows for helpful advice, and Akiko Ukai and Hiromi Mori for technical assistance. This work was in part supported by the National Basic Research Program of China (2015CB943300 to J.Y.W.), the National Natural Science Foundation of China (81373129 and 81571529 to J.Y.W.), and a grant-in-aid for scientific research (C) from Japan Society for the Promotion of Science (25460604 to J.Y.W.).

PY - 2016/3/3

Y1 - 2016/3/3

N2 - 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.

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EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity

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