Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA.
Immunol Res. 2013 Mar;55(1-3):287-97. doi: 10.1007/s12026-012-8369-4.
More than a decade ago, activation-induced deaminase (AID) was identified as the initiator for somatic hypermutation (SHM) and class switch recombination (CSR). Since then, tremendous progress has been achieved toward elucidating how AID functions. AID targets the highly repetitive switch regions of the immunoglobulin heavy chain (IgH) locus to induce DNA double-strand breaks (DSBs), which can be rejoined, leading to switch of constant regions of antibody. When targeting to variable region exons of IgH and IgL loci, AID predominantly induces point mutations, termed SHM, resulting in increased affinity of antibody for antigen. While SHM and CSR enhance antibody diversity, AID-initiated DSBs and mutations may predispose B cells to carcinogenesis. This review focuses on the mechanisms that provide the specificity of AID targeting to Ig loci and the role of AID in genomic instability.
十多年前，激活诱导的脱氨酶（AID）被鉴定为体细胞高频突变（SHM）和类别转换重组（CSR）的启动子。从那时起，在阐明 AID 如何发挥作用方面取得了巨大进展。AID 靶向免疫球蛋白重链（IgH）基因座的高度重复的开关区，以诱导 DNA 双链断裂（DSB），这些 DSB 可以重新连接，导致抗体的恒定区发生转换。当靶向 IgH 和 IgL 基因座的可变区外显子时，AID 主要诱导点突变，称为 SHM，从而增加抗体对抗原的亲和力。虽然 SHM 和 CSR 增强了抗体的多样性，但 AID 引发的 DSB 和突变可能使 B 细胞容易发生癌变。本文重点介绍了 AID 靶向 Ig 基因座的特异性的机制以及 AID 在基因组不稳定性中的作用。
