Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Semin Immunol. 2012 Aug;24(4):293-300. doi: 10.1016/j.smim.2012.05.005. Epub 2012 Jun 14.
The creation of a highly diverse antibody repertoire requires the synergistic activity of a DNA mutator, known as activation-induced deaminase (AID), coupled with an error-prone repair process that recognizes the DNA mismatch catalyzed by AID. Instead of facilitating the canonical error-free response, which generally occurs throughout the genome, DNA mismatch repair (MMR) participates in an error-prone repair mode that promotes A:T mutagenesis and double-strand breaks at the immunoglobulin (Ig) genes. As such, MMR is capable of compounding the mutation frequency of AID activity as well as broadening the spectrum of base mutations; thereby increasing the efficiency of antibody maturation. We here review the current understanding of this MMR-mediated process and describe how the MMR signaling cascade downstream of AID diverges in a locus dependent manner and even within the Ig locus itself to differentially promote somatic hypermutation (SHM) and class switch recombination (CSR) in B cells.
高度多样化的抗体库的产生需要一种称为激活诱导脱氨酶（AID）的 DNA 突变体的协同活性，以及一种能够识别 AID 催化的 DNA 错配的易错修复过程。DNA 错配修复（MMR）不促进通常发生在整个基因组中的典型无差错反应，而是参与促进 Ig 基因中 A:T 突变和双链断裂的易错修复模式。因此，MMR 能够增加 AID 活性的突变频率，并拓宽碱基突变谱；从而提高抗体成熟的效率。我们在这里回顾了对这种 MMR 介导过程的现有认识，并描述了 AID 下游的 MMR 信号级联如何以依赖于基因座的方式以及甚至在 Ig 基因座本身内发散，以在 B 细胞中差异地促进体细胞高频突变（SHM）和类别转换重组（CSR）。
