タキザワ　マキコ   TAKIZAWA Makiko   滝沢　牧子    所属   埼玉医科大学  医学部 総合医療センター　医療安全管理学    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development
掲載誌名	正式名：journal of experimental medicine ISSNコード：0022-1007/1540-9538
出版社	ROCKEFELLER UNIV PRESS
巻・号・頁	205(9),1949-1957頁
著者・共著者	Makiko Takizawa,Helena Tolarova,Zhiyu Li,Wendy Dubois,Susan Lim,Elsa Callen,Sonia Franco,Maria Mosaico,Lionel Feigenbaum,Frederick W. Alt,Andre Nussenzweig,Michael Potter,Rafael Casellas
発行年月	2008/09
概要	Immunoglobulin (Ig) isotype switching is a recombination event that changes the constant domain of antibody genes and is catalyzed by activation-induced cytidine deaminase (AID). Upon recruitment to Ig genes, AID deaminates cytidines at switch (S) recombination sites, leading to the formation of DNA breaks. In addition to their role in isotype switching, AID-induced lesions promote Igh-cMyc chromosomal translocations and tumor development. However, cMyc translocations are also present in lymphocytes from healthy humans and mice, and thus, it remains unclear whether AID directly contributes to the dynamics of B cell transformation. Using a plasmacytoma mouse model, we show that AID(+/-) mice have reduced AID expression levels and display haploinsufficiency both in the context of isotype switching and plasmacytomagenesis. At the Ig loci, AID(+/-) lymphocytes show impaired intra- and inter-switch recombination, and a substantial decrease in the frequency of S mutations and chromosomal breaks. In AID(+/-) mice, these defects correlate with a marked decrease in the accumulation of B cell clones carrying Igh-cMyc translocations during tumor latency. These results thus provide a causality link between the extent of AID enzymatic activity, the number of emerging Igh-cMyc-translocated cells, and the incidence of B cell transformation.
DOI	10.1084/jem.20081007
PermalinkURL	http://rupress.org/jem/article-pdf/205/9/1949/1009943/jem_20081007.pdf