title: Early appearance of germinal center-derived memory B cells and plasma cells in blood after primary immunization.
abstract: Immunization with a T cell-dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated V(H) genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1-expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220(+) memory B cells, and this is sufficient to account for the process of affinity maturation.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Blink
authors.forename: Amanda
authors.initials: A
authors.lastname: Light
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000276:immunology; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006241:Haptens; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D010950:Plasma Cells / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology
chemical_list: C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D018941:Antigens, CD19; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D006241:Haptens; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C026242:4-hydroxy-5-nitrophenyl acetic acid; D006433:Hemocyanins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017493:Leukocyte Common Antigens