title: Presentation of high antigen-dose by splenic B220(lo) B cells fosters a feedback loop between T helper type 2 memory and antibody isotype switching.
abstract: Effective humoral immunity ensues when antigen presentation by B cells culminates in productive cooperation with T lymphocytes. This collaboration, however, remains ill-defined because naive antigen-specific B cells are rare and difficult to track in vivo. Herein, we used a defined transfer model to examine how B lymphocytes, as antigen-presenting cells, shape the development of T-cell memory suitable for generation of relevant antibody responses. Specifically, we examined how B cells presenting different doses of antigen during the initial priming phase shape the development of CD4 T-cell memory and its influence on humoral immunity. The findings indicate that B cells presenting low dose of antigen favour the development of T helper type 1 (Th1) type memory, while those presenting a high antigen dose yielded better Th2 memory cells. The memory Th2 cells supported the production of antibodies by effector B cells and promoted isotype switching to IgG1. Moreover, among the B-cell subsets tested for induction of Th2 memory, the splenic but not peritoneal B220(lo) cells were most effective in sustaining Th2 memory development as well as immunoglobulin isotype switching, and this function involved a tight control by programmed death 1-programmed death ligand 2 interactions.
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, MO, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, MO, USA.
authors.forename: F Betul
authors.initials: FB
authors.lastname: Guloglu
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, MO, USA.|Department of Child Health, University of Missouri School of Medicine, Columbia, MO, USA.|Department of Neurology, University of Missouri School of Medicine, Columbia, MO, USA.
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D015848:Interleukin-5 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011485:Protein Binding; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D015848:Interleukin-5; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D017493:Leukocyte Common Antigens
keywords: B cells; T/B-cell collaboration; antigen presentation; co-stimulatory molecules