title: CD40L is transferred to antigen-presenting B cells during delivery of T-cell help.
abstract: The delivery of T-cell help to B cells is antigen-specific, MHC-restricted, and CD40L (CD154) dependent. It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T-cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. By adding fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells, we discovered that CD40L does not remain on the surface of the T cell, but it is transferred to and endocytosed by B cells receiving T-cell help. In the presence of anti-CD40L antibody, transferred CD40L is nearly absent on bystander B cells that are not presenting antigen, and the bystander cells do not become activated. Because transfer of CD40L to B cells correlates with B-cell activation, we speculate that persistence of helper T-cell-derived CD40L on or in B cells could permit sustained CD40 signaling enabling survival and proliferation of antigen-presenting B cells following brief interactions with helper T cells in vivo in germinal centers.
authors.affiliation: Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gardell
authors.affiliation: Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Parker
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002450:Cell Communication; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging; D021381:Protein Transport; D015398:Signal Transduction; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D019013:CD40 Antigens; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand
keywords: CD154; CD40 ligand; CD40L; Immunological synapse; Membrane transfer; T-cell help