論文

査読有り
2017年5月

Mouse model of Epstein-Barr virus LMP1-and LMP2A-driven germinal center B-cell lymphoproliferative disease

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Takeharu Minamitani
  • ,
  • Yijie Ma
  • ,
  • Hufeng Zhou
  • ,
  • Hiroshi Kida
  • ,
  • Chao-Yuan Tsai
  • ,
  • Masanori Obana
  • ,
  • Daisuke Okuzaki
  • ,
  • Yasushi Fujio
  • ,
  • Atsushi Kumanogoh
  • ,
  • Bo Zhao
  • ,
  • Hitoshi Kikutani
  • ,
  • Elliott Kieff
  • ,
  • Benjamin E. Gewurz
  • ,
  • Teruhito Yasui

114
18
開始ページ
4751
終了ページ
4756
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1701836114
出版者・発行元
NATL ACAD SCIENCES

Epstein-Barr virus (EBV) is a major cause of immunosuppression-related B-cell lymphomas and Hodgkin lymphoma (HL). In these malignancies, EBV latent membrane protein 1 (LMP1) and LMP2A provide infected B cells with surrogate CD40 and B-cell receptor growth and survival signals. To gain insights into their synergistic in vivo roles in germinal center (GC) B cells, from which most EBV-driven lymphomas arise, we generated a mouse model with conditional GC B-cell LMP1 and LMP2A coexpression. LMP1 and LMP2A had limited effects in immunocompetent mice. However, upon T- and NK-cell depletion, LMP1/2A caused massive plasmablast outgrowth, organ damage, and death. RNA-sequencing analyses identified EBV oncoprotein effects on GC B-cell target genes, including up-regulation of multiple proinflammatory chemokines and master regulators of plasma cell differentiation. LMP1/2A coexpression also up-regulated key HL markers, including CD30 and mixed hematopoietic lineage markers. Collectively, our results highlight synergistic EBV membrane oncoprotein effects on GC B cells and provide a model for studies of their roles in immunosuppression-related lymphoproliferative diseases.

Web of Science ® 被引用回数 : 19

リンク情報
DOI
https://doi.org/10.1073/pnas.1701836114
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28351978
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000400358000056&DestApp=WOS_CPL