title: Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination.
abstract: The primary antibody repertoire is generated by mechanisms involving the assembly of the exons that encode the antigen-binding variable regions of immunoglobulin heavy (IgH) and light (IgL) chains during the early development of B lymphocytes. After antigen-dependent activation, mature B lymphocytes can further alter their IgH and IgL variable region exons by the process of somatic hypermutation (SHM), which allows the selection of B cells in which SHMs resulted in the production of antibodies with increased antigen affinity. In addition, during antigen-dependent activation, B cells can also change the constant region of their IgH chain through a DNA double-strand-break (DSB) dependent process referred to as IgH class switch recombination (CSR), which generates B cell progeny that produce antibodies with different IgH constant region effector functions that are best suited for a elimination of a particular pathogen or in a particular setting. Both the mutations that underlie SHM and the DSBs that underlie CSR are initiated in target genes by activation-induced cytidine deaminase (AID). This review describes in depth the processes of SHM and CSR with a focus on mechanisms that direct AID cytidine deamination in activated B cells and mechanisms that promote the differential outcomes of such cytidine deamination.
authors.affiliation: Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Joyce K
authors.initials: JK
authors.lastname: Hwang
authors.affiliation: Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.affiliation: Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Leng-Siew
authors.initials: LS
authors.lastname: Yeap
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D000906:Antibodies