title: The extent of affinity maturation differs between the memory and antibody-forming cell compartments in the primary immune response.
abstract: Immunization with protein-containing antigens results in two types of antigen-specific B cell: antibody forming cells (AFCs) producing antibody of progressively higher affinity and memory lymphocytes capable of producing high affinity antibody upon re-exposure to antigen. The issue of the inter-relationship between affinity maturation of memory B cells and AFCs was addressed through analysis of single, antigen-specific B cells from the memory and AFC compartments during the primary response to a model antigen. Only 65% of splenic memory B cells were found capable of producing high affinity antibody, meaning that low affinity cells persist into this compartment. In contrast, by 28 days after immunization all AFCs produced high affinity antibody. We identified a unique, persistent sub-population of bone marrow AFCs containing few somatic mutations, suggesting they arose early in the response, yet highly enriched for an identical affinity-enhancing amino acid exchange, suggesting strong selection. Our results imply that affinity maturation of a primary immune response occurs by the early selective differentiation of high affinity variants into AFCs which subsequently persist in the bone marrow. In contrast, the memory B-cell population contains few, if any, cells from the early response and is less stringently selected.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
authors.forename: K G
authors.initials: KG
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Light
authors.forename: G J
authors.initials: GJ
authors.lastname: Nossal
authors.forename: D M
authors.initials: DM
authors.lastname: Tarlinton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014611:Vaccination
chemical_list: D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid