title: Both mutated and unmutated memory B cells accumulate mutations in the course of the secondary response and develop a new antibody repertoire optimally adapted to the secondary stimulus.
abstract: High-affinity memory B cells are preferentially selected during secondary responses and rapidly differentiate into antibody-producing cells. However, it remains unknown whether only high-affinity, mutated memory B cells simply expand to dominate the secondary response or if in fact memory B cells with a diverse VH repertoire, including those with no mutations, accumulate somatic mutations to create a new repertoire through the process of affinity maturation. In this report, we took a new approach to address this question by analyzing the VH gene repertoire of IgG1(+) memory B cells before and after antigen re-exposure in a host unable to generate IgG(+) B cells. We show here that both mutated and unmutated IgG1(+) memory B cells respond to secondary challenge and expand while accumulating somatic mutations in their VH genes in a stepwise manner. Both types of memory cells subsequently established a VH gene repertoire dominated by two major clonotypes, which are distinct from the original repertoire before antigen re-exposure. In addition, heavily mutated memory B cells were excluded from the secondary repertoire. Thus, both mutated and unmutated IgG1(+) memory cells equally contribute to establish a new antibody repertoire through a dynamic process of mutation and selection, becoming optimally adapted to the recall challenge.
authors.affiliation: Laboratory for Immunological Memory, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaji
authors.forename: Koji
authors.initials: K
authors.lastname: Furukawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishige
authors.forename: Itsumi
authors.initials: I
authors.lastname: Toyokura
authors.forename: Masaki
authors.initials: M
authors.lastname: Nomura
authors.forename: Mariko
authors.initials: M
authors.lastname: Okada
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimoda
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: Antibody repertoire; memory B cells; secondary response; somatic hypermutation
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