Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation.

Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation.
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激活诱导的脱氨酶(AID)在免疫球蛋白SMU区域中指导的超名:在类开关重组和体细胞超伪装的共同步骤中,援助参与的意义。

DOI:
10.1084/jem.20012144
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发表时间:
2002-02-18
影响因子:
15.3
通讯作者:
Honjo, Tasuku
Honjo, Tasuku
中科院分区:
医学1区
文献类型:
--
作者:
Nagaoka, Hitoshi;Muramatsu, Masamichi;Yamamura, Namiko;Kinoshita, Kazuo;Honjo, Tasuku

文献摘要

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体细胞超突变和类切换重组分别导致B淋巴细胞免疫球蛋白基因不同区域的突变:可变区的点突变和S区的大缺失。然而,两者都依赖于激活诱导脱氨酶(AID),AID在这两个反应中的作用一直是个谜。在这里,我们报告了诱导CSR而不是SHM的B细胞刺激,导致依赖艾滋病的SHM样点突变在开关μ区域积累,与CSR解偶联。这些发现有力地表明,AID本身或AID的RNA编辑功能产生的单个分子可能介导了SHM和CSR的共同步骤,这可能参与了DNA的切割。
Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. Yet both depend on activation-induced deaminase (AID), the function of which in the two reactions has been an enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch μ region, uncoupled with CSR. These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage.