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, Kouji Hase, Ji Yang Wang

Research output: Contribution to journalArticle

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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 languageEnglish
Article number10836
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016 Mar 3

Fingerprint

Germinal Center
apoptosis
Autoimmunity
B-Lymphocytes
Cells
Apoptosis
Humoral Immunity
collagens
Immunization
antibodies
Self Tolerance
mice
Collagen Type II
Antibodies
Rheumatoid Factor
Transcription
Autoantibodies
Androgens
Arthritis
Antibody Formation

ASJC Scopus subject areas

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

Cite this

EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity. / Li, Yingqian; Takahashi, Yoshimasa; Fujii, Shin Ichiro; Zhou, Yang; Hong, Rongjian; Suzuki, Akari; Tsubata, Takeshi; Hase, Kouji; Wang, Ji Yang.

In: Nature Communications, Vol. 7, 10836, 03.03.2016.

Research output: Contribution to journalArticle

Li, Yingqian ; Takahashi, Yoshimasa ; Fujii, Shin Ichiro ; Zhou, Yang ; Hong, Rongjian ; Suzuki, Akari ; Tsubata, Takeshi ; Hase, Kouji ; Wang, Ji Yang. / EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity. In: Nature Communications. 2016 ; Vol. 7.
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