Somatic Hypermutation in Antibody Evolution

Abstract Somatic hypermutation (SHM) of immunoglobulin ( Ig ) genes is a major mechanism for amplifying the antibody repertoire of vertebrates. SHM results in high frequencies of point mutations in the variable region of Ig genes, the region encoding the antigen‐binding domain of antibodies. The constant region is spared, ensuring conservation of the biological functions of antibodies. We briefly review the biology of SHM and its molecular hallmarks. We discuss what is known and what remains to be investigated of the molecular process that creates the mutations, including the properties, normal and aberrant functions of the activation induced deoxy‐cytidine deaminase, AID, the enzyme that initiates SHM.