Luo Sha, Qiao Ruolin, Zhang Xuefei
Biomedical Pioneering Innovation Center, Innovation Center for Genomics, Peking University, Beijing, China.
Academy for Advanced Interdisciplinery Studies, Peking University, Beijing, China.
Front Cell Dev Biol. 2022 May 17;10:884873. doi: 10.3389/fcell.2022.884873. eCollection 2022.
The diversification of B-cell receptor (BCR), as well as its secreted product, antibody, is a hallmark of adaptive immunity, which has more specific roles in fighting against pathogens. The antibody diversification is from recombination-activating gene (RAG)-initiated V(D)J recombination, activation-induced cytidine deaminase (AID)-initiated class switch recombination (CSR), and V(D)J exon somatic hypermutation (SHM). The proper repair of RAG- and AID-initiated DNA lesions and double-strand breaks (DSBs) is required for promoting antibody diversification, suppressing genomic instability, and oncogenic translocations. DNA damage response (DDR) factors and DSB end-joining factors are recruited to the RAG- and AID-initiated DNA lesions and DSBs to coordinately resolve them for generating productive recombination products during antibody diversification. Recently, cohesin-mediated loop extrusion is proposed to be the underlying mechanism of V(D)J recombination and CSR, which plays essential roles in promoting the orientation-biased deletional end-joining . Here, we will discuss the mechanism of DNA damage repair in antibody diversification.
B细胞受体（BCR）及其分泌产物抗体的多样化是适应性免疫的一个标志，适应性免疫在对抗病原体方面具有更特定的作用。抗体多样化源于重组激活基因（RAG）启动的V（D）J重组、激活诱导的胞苷脱氨酶（AID）启动的类别转换重组（CSR）以及V（D）J外显子体细胞超突变（SHM）。促进抗体多样化、抑制基因组不稳定和致癌易位需要对RAG和AID启动的DNA损伤及双链断裂（DSB）进行适当修复。DNA损伤应答（DDR）因子和DSB末端连接因子被招募到RAG和AID启动的DNA损伤及DSB处，以协调解决这些问题，从而在抗体多样化过程中产生有效的重组产物。最近，黏连蛋白介导的环挤压被认为是V（D）J重组和CSR的潜在机制，其在促进定向偏向性缺失末端连接中起重要作用。在此，我们将讨论抗体多样化过程中DNA损伤修复的机制。
