title: AID targeting in antibody diversity.
abstract: Antibody maturation requires class switch recombination (CSR) and somatic hypermutation (SHM), both of which are initiated by activation-induced cytidine deaminase (AID). AID deaminates cytosine residues resulting in mismatches that are differentially processed to produce double-strand breaks in Ig switch (S) regions that lead to CSR, or to point mutations in variable (V) exons resulting in SHM. Although AID was first thought to be Ig-specific, recent work indicates that it also targets a diverse group of non-Ig loci, including genes such as Bcl6 and c-myc, whose modification by AID results in lymphoma-associated mutations and translocations. Here, we review the recent literature on AID targeting and the role for transcriptional stalling in recruitment of this enzyme to Ig and non-Ig loci. We propose a model for AID recruitment based on transcriptional stalling, which reconciles several of the key features of SHM, CSR, and lymphoma-associated translocation.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, USA.
authors.forename: Rushad
authors.initials: R
authors.lastname: Pavri
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D000916:Antibody Diversity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase