Franklin Andrew, Blanden Robert V
Biocontrol Group, School of Botany and Zoology, Australian National University, Daley Road, Acton, ACT 0200, Australia.
Trends Biochem Sci. 2006 May;31(5):252-8. doi: 10.1016/j.tibs.2006.03.008. Epub 2006 Apr 17.
The "affinity maturation" of the humoral immune response is driven by antigen-activated somatic hypermutation (SHM) of the genes that encode antibody variable regions and the subsequent antigenic selection of mutant clones. The molecular mechanism of SHM is yet to be completely elucidated. SHM affects cytosine-guanine (C/G) and adenine-thymine (A/T) pairs with approximately equal frequency in vivo. The proposition that error-prone DNA-dependent DNA synthesis explains A/T-targeted hypermutagenesis seems to have mainstream support within the hypermutation research community at present. A major feature of SHM in vivo is that C/G hypermutation is strand unbiased, whereas A/T hypermutation is strand biased. We show that the "DNA-based polymerase error" model of A/T-targeted hypermutagenesis does not explain this important aspect of SHM.
体液免疫反应的“亲和力成熟”由抗原激活的编码抗体可变区基因的体细胞高频突变（SHM）以及随后对突变克隆的抗原选择所驱动。SHM的分子机制尚未完全阐明。在体内，SHM对胞嘧啶-鸟嘌呤（C/G）和腺嘌呤-胸腺嘧啶（A/T）碱基对的影响频率大致相等。目前，易错DNA依赖性DNA合成解释A/T靶向超突变的观点似乎在超突变研究领域得到了主流支持。体内SHM的一个主要特征是C/G超突变无链偏向性，而A/T超突变具有链偏向性。我们发现，A/T靶向超突变的“基于DNA的聚合酶错误”模型无法解释SHM的这一重要方面。
