Somatic Hypermutation of Immunoglobulin Genes: Merging Mechanisms for Genetic Diversity

Somatic hypermutation is critical for the generation of high-affinity antibodies and effective immune responses, but its molecular mechanism remains poorly understood. Recent studies have identified DNA strand lesions associated with the hypermutation process and suggested the involvement of specific repair molecules and pathways. Particularly exciting has been the discovery of a putative RNA editing enzyme, the activation-induced cytidine deaminase (AID), that is required for all immunoglobulin gene-specific modification reactions (somatic hypermutation, class switch recombination, and gene conversion). Parallels between these three reactions are considered in light of recent advances.