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B 细胞免疫与癌症中的激活诱导胞苷脱氨酶。

Activation-induced Cytidine Deaminase in B Cell Immunity and Cancers.

机构信息

Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718, Korea.

出版信息

Immune Netw. 2012 Dec;12(6):230-9. doi: 10.4110/in.2012.12.6.230. Epub 2012 Dec 31.

Abstract

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.

摘要

激活诱导胞嘧啶脱氨酶(AID)是一种主要在生发中心 B 细胞中表达的酶,在免疫球蛋白类别转换重组和体细胞超突变中发挥关键作用,从而促进抗体(Ab)成熟。这两个遗传过程使 Ab 具有在体液免疫反应中针对多种抗原(病原体)的保护功能。在 B 细胞中,AID 的表达受到 AID 基因座转录激活或 AID mRNA 转录后抑制的调节。此外,AID 的稳定和靶向取决于翻译后修饰以及与其他细胞/核因子的相互作用。另一方面,AID 的异常表达会导致 B 细胞白血病和淋巴瘤,包括由 c-myc/IgH 易位引起的伯基特淋巴瘤。AID 还异位表达于 T 细胞和非免疫细胞中,并在相关 DNA 位点引发点突变,导致肿瘤形成。在这里,我回顾了关于 AID 功能、AID 表达调控、B 细胞中 AID 的稳定性和靶向性以及 AID 相关肿瘤形成的最新文献。

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