論文

査読有り
2015年9月

Evasion of affinity-based selection in germinal centers by Epstein-Barr virus LMP2A

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Takeharu Minamitani
  • ,
  • Teruhito Yasui
  • ,
  • Yijie Ma
  • ,
  • Hufeng Zhou
  • ,
  • Daisuke Okuzaki
  • ,
  • Chiau-Yuang Tsai
  • ,
  • Shuhei Sakakibara
  • ,
  • Benjamin E. Gewurz
  • ,
  • Elliott Kieff
  • ,
  • Hitoshi Kikutani

112
37
開始ページ
11612
終了ページ
11617
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1514484112
出版者・発行元
NATL ACAD SCIENCES

Epstein-Barr virus (EBV) infects germinal center (GC) B cells and establishes persistent infection in memory B cells. EBV-infected B cells can cause B-cell malignancies in humans with T- or natural killer-cell deficiency. We now find that EBV-encoded latent membrane protein 2A (LMP2A) mimics B-cell antigen receptor (BCR) signaling in murine GC B cells, causing altered humoral immune responses and autoimmune diseases. Investigation of the impact of LMP2A on B-cell differentiation in mice that conditionally express LMP2A in GC B cells or all B-lineage cells found LMP2A expression enhanced not only BCR signals but also plasma cell differentiation in vitro and in vivo. Conditional LMP2A expression in GC B cells resulted in preferential selection of low-affinity antibody-producing B cells despite apparently normal GC formation. GC B-cell-specific LMP2A expression led to systemic lupus erythematosus-like autoimmune phenotypes in an age-dependent manner. Epigenetic profiling of LMP2A B cells found increased H3K27ac and H3K4me1 signals at the zinc finger and bric-a-brac, tramtrack domain-containing protein 20 locus. We conclude that LMP2A reduces the stringency of GC B-cell selection and may contribute to persistent EBV infection and pathogenesis by providing GC B cells with excessive prosurvival effects.

Web of Science ® 被引用回数 : 28

リンク情報
DOI
https://doi.org/10.1073/pnas.1514484112
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26305967
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000361393700056&DestApp=WOS_CPL
ID情報
  • DOI : 10.1073/pnas.1514484112
  • ISSN : 0027-8424
  • PubMed ID : 26305967
  • Web of Science ID : WOS:000361393700056

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