ウエダ　ヨシヒロ   UEDA YOSHIHIRO   植田　祥啓    所属   関西医科大学  附属生命医学研究所分子遺伝学部門    職種   准教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	Activation-Induced Cytidine Deaminase Expression and Activity in the Absence of Germinal Centers: Insights into Hyper-IgM Syndrome.
掲載誌名	正式名：Journal of Immunology 略　 称：J. Immunol
巻・号・頁	183(5),pp.-
著者・共著者	Masayuki Kuraoka, Dongmei Liao, Kaiyong Yang, Sallie D. Allgood, Marc C. Levesque, Garnett Kelsoe, and Yoshihiro Ueda
担当区分	最終著者
発行年月	2009/09
概要	omatic hypermutation normally occurs as a consequence of the expression of activation-induced cytidine deaminase (AID) by Ag-activated, mature B cells during T cell-dependent germinal center responses. Nonetheless, despite their inability to express CD154 and initiate GC responses, patients with type 1 hyper-IgM syndrome (HIGM1) support populations of IgM+IgD+CD27+ B cells that express mutated Ig genes. The origin of these mutated B cells is unknown; the IgM+IgD+CD27+ cells do not express AID and appear to acquire mutations independent of stringent selection by Ag. Here, we demonstrate that immature/transitional 1 B cells from the bone marrow of CD154-deficient mice express AID and acquire Ig mutations that lack the hallmarks of antigenic selection via BCR signaling. Comparable levels of AID expression was found in developmentally immature B cells recovered from murine fetal liver and from human immature/transitional 1 B cells recovered from umbilical cord blood. AID expression in human fetal liver was also robust, approaching that of human tonsil tissue and the human germinal center B cell line, Ramos. These observations led us to conclude that AID expression in developing human B cells is the origin of the mutated IgM+IgD+CD27+ B cells present in HIGM1 patients, and we propose that both mice and humans share a latent, AID-dependent pathway for the preimmune diversification of B lymphocytes that is more prominent in chicken, sheep, and rabbits.