Immunology Program, Memorial Sloan-Kettering Cancer Center, Gerstner Sloan-Kettering Graduate School, 1275 York Avenue, New York, NY 10065, United States.
Semin Immunol. 2012 Aug;24(4):264-72. doi: 10.1016/j.smim.2012.05.006. Epub 2012 Jul 6.
Protective humoral immune responses result from immunoglobulin (Ig) diversification reactions that proceed through programmed DNA double-strand breaks and mutations in developing or mature B cells. While primary Ig diversity is dependent on V(D)J recombination and the RAG proteins, secondary diversification is achieved through class switch recombination (CSR) and somatic hypermutation (SHM), which require AID (activation induced deaminase). Because aberrant AID activity can result in mutations in non-Ig loci and DNA translocations between the Ig locus and non-Ig genes, the activity of AID must be stringently regulated. AID mRNA expression is regulated transcriptionally by cytokine stimulation and post-transcriptionally by miRNAs. AID activity is regulated by post-translational modifications, subcellular localization, and interaction with other proteins. All of these molecular mechanisms have evolved to specifically induce AID-dependent mutations and DNA double-strand breaks at the Ig loci to promote maximal Ig gene diversification while limiting the access of this mutator to non-Ig regions.
保护性体液免疫应答源自免疫球蛋白（Ig）的多样化反应，该反应通过程序性 DNA 双链断裂和发育或成熟 B 细胞中的突变进行。虽然初级 Ig 多样性依赖于 V(D)J 重组和 RAG 蛋白，但次级多样化是通过类别转换重组（CSR）和体细胞超突变（SHM）实现的，这需要 AID（激活诱导的脱氨酶）。由于异常的 AID 活性可导致非 Ig 基因座的突变和 Ig 基因座与非 Ig 基因之间的 DNA 易位，因此 AID 的活性必须受到严格调控。AID mRNA 的表达受细胞因子刺激的转录调控和 miRNA 的转录后调控。AID 活性受到翻译后修饰、亚细胞定位和与其他蛋白质相互作用的调节。所有这些分子机制的进化都是为了在 Ig 基因座特异性诱导 AID 依赖性突变和 DNA 双链断裂，以促进最大的 Ig 基因多样化，同时限制这种诱变剂进入非 Ig 区域。
