title: Molecular Mechanisms of Somatic Hypermutation and Class Switch Recombination.
abstract: In order to promote an efficient humoral immune response, germinal center B cells modify both the antigen recognition and effector domains by programmed genetic alterations of their antibody genes. To do so, B cells use the enzyme activation-induced deaminase (AID), which transforms deoxycytidine into deoxyuridine at the immunoglobulin genes, triggering mutagenic DNA repair. Data accumulated during the past decade have significantly advanced our understanding of how AID activity is regulated and preferentially targeted to the immunoglobulin genes. There is also a better understanding of the ways by which AID-catalyzed uracil is recognized and the ensuing downstream processing underpinning the mechanisms of somatic hypermutation and class switch recombination. Here, we critically review these advances in the context of their relevance for the humoral immune response. A detailed understanding of these molecular mechanisms is paramount to uncover the basis of B cell intrinsic immunodeficiency, as well as to suggest tools and strategies that might allow boosting antibody gene diversification in the context of immunizations or infections that require the elicitation of rare or highly mutated antibody variants.
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada; Mcgill University, Montreal, QC, Canada. Electronic address: stephenpatrick.methot@ircm.qc.ca.
authors.forename: S P
authors.initials: SP
authors.lastname: Methot
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada; Mcgill University, Montreal, QC, Canada; Université de Montréal, Montreal, QC, Canada. Electronic address: javier.di.noia@ircm.qc.ca.
authors.forename: J M
authors.initials: JM
authors.lastname: Di Noia
mesh_terms: D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D003564:Cytidine Deaminase; D006801:Humans; D056724:Immunity, Humoral; D017578:Immunoglobulin Class Switching; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: Activation-induced deaminase; Antibody response; B-lymphocytes; Class switch recombination; DNA double strand break repair; Germinal center; Immunoglobulin gene conversion; Mismatch DNA repair; Somatic hypermutation; Uracil-DNA glycosylase