Immunoglobulin Somatic Hypermutation

The immunoglobulin (Ig) repertoire achieves functional diversification through several somatic alterations of the Ig locus. One of these processes, somatic hypermutation (SHM), deposits point mutations into the variable region of the Ig gene to generate higher-affinity variants. Activation-induced cytidine deaminase (AID) converts cytidine to uridine to initiate the hypermutation process. Error-prone versions of DNA repair are believed to then process these lesions into a diverse spectrum of point mutations. We review the current understanding of the molecular mechanisms and regulation of SHM, and also discuss emerging ideas which merit further exploration.