AID in Antibody Diversification: There and Back again

Feng, Yuqing; Seija, Noé; Di Noia, Javier; Martin, Alberto

Abstract Activation-Induced cytidine Deaminase (AID) initiates affinity maturation and isotype switching by deaminating deoxycytidines within immunoglobulin genes, leading to somatic hypermutation and class switch recombination. AID thus potentiates the humoral response to clear pathogens. Marking the 20th anniversary of the discovery of AID, we synthesize 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 repair pathway during class switch recombination. 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.