論文

査読有り
2015年2月

Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Rashmi Kumar
  • ,
  • P. Bach
  • ,
  • Federica Mainoldi
  • ,
  • Mikako Maruya
  • ,
  • Satoshi Kishigami
  • ,
  • Hassan Jumaa
  • ,
  • Teruhiko Wakayama
  • ,
  • Osami Kanagawa
  • ,
  • Sidonia Fagarasan
  • ,
  • Stefano Casola

112
5
開始ページ
E450
終了ページ
E457
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1417988112
出版者・発行元
NATL ACAD SCIENCES

In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe V(H)Q52(NT); V kappa gr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In V(H)Q52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In V(H)Q52(NT) animals, over 20% of mature B cells disrupted the single productive, non-autoimmune IgH rearrangement through VH replacement and exchanged it with a highly diversified pool of IgH specificities. VH replacement occurred in early pro-B cells, was independent of pre-B-cell receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH replacement was also identified in 5% of peripheral B cells of mice inheriting a different productive VH rearrangement expressed in the form of an IgM H chain. In summary, editing of a productive IgH rearrangement through VH replacement can account for up to 20% of the IgH repertoire expressed by mature B cells.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1073/pnas.1417988112
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25609671
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000349087700011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1073/pnas.1417988112
  • ISSN : 0027-8424
  • PubMed ID : 25609671
  • Web of Science ID : WOS:000349087700011

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