Class-switch recombination: after the dawn of AID.
Isotype class switching is central to the humoral immune response. The discovery that mutations in the activation-induced deaminase (AID) gene inhibit class-switch recombination, somatic hypermutation and gene conversion is a major step forward in defining the underlying mechanisms of these gene modification events. The propensity of mutations to occur at dC/dG nucleotides during somatic hypermutation and the homology between AID and cytidine deaminase has resulted in studies demonstrating that AID has the properties of a cytidine-specific mutator and also that elements of the base-excision repair pathway play a central role in class switching and hypermutation. AID is not a promiscuous mutator in the B cell, suggesting that there are specific molecular targeting mechanisms that regulate the accessibility of DNA to AID and differentially regulate class-switch recombination and somatic hypermutation. During class switching, isotype-specific targeting occurs independently of AID and provides another level of specificity to this recombination event.
Kenter
Amy L
AL
Department of Microbiology and Immunology, University of Illinois College of Medicine, 835 South Wolcott Avenue, Chicago, IL 60680, USA. star1@uic.edu
D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D005785:Gene Conversion; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase