Department of Immunology, University of Toronto, Toronto, ON, Canada.
Institute de Recherches Cliniques de Montréal, Montréal, QC, Canada; Molecular Biology Programs, Department of Medicine, University of Montreal, Montréal, QC, Canada.
Trends Immunol. 2020 Jul;41(7):586-600. doi: 10.1016/j.it.2020.04.009. Epub 2020 Apr 27.
Activation-Induced cytidine Deaminase (AID) initiates affinity maturation and isotype switching by deaminating deoxycytidines within immunoglobulin genes, leading to somatic hypermutation (SHM) and class switch recombination (CSR). AID thus potentiates the humoral response to clear pathogens. Marking the 20th anniversary of the discovery of AID, we review the current understanding of AID function. We discuss AID biochemistry and how error-free forms of DNA repair are co-opted to prioritize mutagenesis over accuracy during antibody diversification. We discuss the regulation of DNA double-strand break (DSB) repair pathways during CSR. We describe genomic targeting of AID as a multilayered process involving chromatin architecture, cis- and trans-acting factors, and determining mutagenesis - distinct from AID occupancy at loci that are spared from mutation.
激活诱导胞嘧啶脱氨酶 (AID) 通过脱氨脱氧胞嘧啶启动免疫球蛋白基因中的亲和力成熟和同种型转换，导致体细胞超突变 (SHM) 和类别转换重组 (CSR)。因此，AID 增强了清除病原体的体液反应。在发现 AID 20 周年之际，我们回顾了目前对 AID 功能的理解。我们讨论了 AID 的生物化学特性，以及如何将无错误形式的 DNA 修复机制共同用于在抗体多样化过程中优先进行突变而不是准确性。我们讨论了 CSR 过程中 DNA 双链断裂 (DSB) 修复途径的调节。我们将 AID 的基因组靶向描述为一个多层次的过程，涉及染色质结构、顺式和反式作用因子，并决定突变，这与 AID 在免受突变的基因座上的占据不同。
