Immunoglobulin gene conversion: synthesizing antibody diversification and DNA repair

Recent developments in the field of antibody (Ab) diversification have rapidly advanced our understanding of the molecular mechanism underlying these events. Key to these developments was the identification of activation-induced cytidine deaminase (AID) as the central regulator of secondary Ab diversification, and the elucidation of its primary function as a DNA deaminase. Incredibly, current literature suggests the existence of a shared pathway, common to all secondary diversification processes, from which the separate outcomes branch outwards at various points. Immunoglobulin gene conversion (IGC) is one of these mechanisms and is used by a number of vertebrate species in both the development of the pre-immune repertoire and in affinity maturation. In a manner similar to other Ab diversification mechanisms, IGC has managed to co-opt a normal DNA repair pathway for the generation of receptor diversity. In the case of IGC specifically, that pathway is homologous recombination (HR). A burgeoning wealth of genetic, biochemical and structural data has clarified the roles of many key HR factors, allowing new insight into its molecular mechanism. These insights, combined with those from the common mechanism of AID action, synergize to develop an emerging picture of the mechanism underlying IGC.