title: Somatic hypermutation shapes the antibody repertoire of memory B cells in humans.
abstract: High-affinity antibodies produced by memory B cells differ from antibodies produced in naive B cells in two respects. First, many of these antibodies show somatic hypermutation, and second, the repertoire of antibodies expressed in memory responses is highly selected. To determine whether somatic hypermutation is responsible for the shift in the antibody repertoire during affinity maturation, we analyzed the immunoglobulin lambda light chain (Iglambda) repertoire expressed by naive and antigen-selected memory B cells in humans. We found that the Iglambda repertoire differs between naive and memory B cells and that this shift in the repertoire does not occur in the absence of somatic hypermutation in patients lacking activation-induced cytidine deaminase (AID). Our work suggests that somatic hypermutation makes a significant contribution to shaping the antigen-selected antibody repertoire in humans.
authors.affiliation: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA.
authors.forename: E
authors.initials: E
authors.lastname: Meffre
authors.forename: N
authors.initials: N
authors.lastname: Catalan
authors.forename: F
authors.initials: F
authors.lastname: Seltz
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: M C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: A
authors.initials: A
authors.lastname: Durandy
mesh_terms: D000071479:APOBEC-1 Deaminase; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007156:Immunologic Memory / Q000235:genetics*; D066298:In Vitro Techniques; D009154:Mutation; D012313:RNA / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D017931:DNA Primers; D007146:Immunoglobulin lambda-Chains; D012313:RNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase