title: CD40-CD40 ligand interactions stimulate B cell antigen processing.
abstract: The interactions between B cell CD40 and T cell CD40 ligand (CD40L) have been shown recently to play an important role in T cell-dependent activation of B cells. Here, we show that the ligation of CD40 stimulates the processing of antigen by B cells. The activation of an antigen-specific T cell hybrid by B cells co-cultured with insect cells expressing recombinant CD40L or with a CD40-specific monoclonal antibody requires less antigen and fewer B cells compared to control cells. The augmentation was observed both for processing initiated by antigen binding to and cross-linking the surface immunoglobulin, and processing of antigen taken up by fluid-phase pinocytosis. CD40 appears to affect a step in the intracellular processing of antigen, as CD40 has no effect on the presentation of an antigenic peptide which does not require processing. In addition, the CD40-induced augmentation of processing is not attributable to the effect of CD40 ligation on the cell surface expression of B7, LFA-1 or CD23. CD40 ligation does not affect the biosynthesis of the class II EK molecules, and although ligation of CD40 induces B cell proliferation, the augmentation of processing does not require proliferation. The ability of CD40 to stimulate B cell antigen processing has the potential to influence significantly the outcome of antigen-dependent T cell-B cell interactions.
authors.affiliation: Department of Biochemistry, Molecular Biology, Northwestern University, Evanston, IL 60208-3500, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Faassen
authors.forename: D P
authors.initials: DP
authors.lastname: Dalke
authors.forename: M T
authors.initials: MT
authors.lastname: Berton
authors.forename: W D
authors.initials: WD
authors.lastname: Warren
authors.forename: S K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D017951:Antigen Presentation / Q000187:drug effects*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism / Q000494:pharmacology*; D023201:CD40 Ligand; D003432:Cross-Linking Reagents; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000737:chemistry; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016393:Lymphoma, B-Cell; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D017434:Protein Structure, Tertiary; D017455:Receptors, IgE / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D003432:Cross-Linking Reagents; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D023201:CD40 Ligand