title: Aborted germinal center reactions and B cell memory by follicular T cells specific for a B cell receptor V region peptide.
abstract: A fundamental problem in immunoregulation is how CD4(+) T cells react to immunogenic peptides derived from the V region of the BCR that are created by somatic mechanisms, presented in MHC II, and amplified to abundance by B cell clonal expansion during immunity. BCR neo Ags open a potentially dangerous avenue of T cell help in violation of the principle of linked Ag recognition. To analyze this issue, we developed a murine adoptive transfer model using paired donor B cells and CD4 T cells specific for a BCR-derived peptide. BCR peptide-specific T cells aborted ongoing germinal center reactions and impeded the secondary immune response. Instead, they induced the B cells to differentiate into short-lived extrafollicular plasmablasts that secreted modest quantities of Ig. These results uncover an immunoregulatory process that restricts the memory pathway to B cells that communicate with CD4 T cells via exogenous foreign Ag.
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, School of Medicine, Denver, CO 80206, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Heiser
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Snyder
authors.forename: James
authors.initials: J
authors.lastname: St Clair
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Wysocki
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D018985:Epitopes, B-Lymphocyte; D006131:Growth Inhibitors; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010455:Peptides; D011947:Receptors, Antigen, B-Cell