Aid, chromatin, and understanding the role of splicing in SHM

Abstract

Antibody diversity is a key event inside B-cells that limits/eliminates pathogens. B-cells produce antibody diversity via VDJ recombination, somatic hypermutation (SHM), and class switch recombination (CSR). Interestingly, activation-induced cytidine deaminase (AID) is the initiator of SHM and CSR. AID mediates its effect by deamination of cytosine to uracil in the variable region (in case of SHM) and the constant region (in case of CSR), resulting in nucleotide mismatch (Fig. 1). Subsequently, AID-created mismatches are repaired in error-prone fashion to give rise high-affinity antibody and isotypic switching. Usually, AID activity is confined to immunoglobulin (Ig) genes, but in many cases, it is reported to be mistargeted to non-Ig genes resulting in deleterious effects. AID mistargeting can lead to B-cell-related malignancy.