Activated T hybridomas induce upregulation of B7-1 on bystander B lymphoma cells by a contact-dependent interaction utilizing CD40 ligand.
The upregulation of costimulatory molecules of antigen presenting cells (APC) resulting from interaction with activated T cells was studied in an in vitro system composed of well-characterized murine T hybridomas and B cell lymphomas. Increased B7-1 expression was induced on both MHC-matched and -mismatched (bystander) B lymphoma cells present in cultures of activated T hybridomas. Identical results were obtained with T hybridomas activated by either the appropriate peptide presented by MHC-matched APC or by mitogen stimulation in the absence of MHC/TCR cognate interactions. Soluble factors alone did not lead to upregulation of B7-1; B lymphomas cultured on the opposite side of a transwell membrane from an ongoing T cell stimulation response, or in supernatants of activated T cells, did not exhibit enhanced expression of B7-1. Antibodies to the CD40 ligand (CD40L) of T cells inhibited the increased appearance of B7-1 on B lymphomas. Significant B7-1 upregulation on the population of bystander B cells could be achieved even when they were present at a 10:1 excess over MHC-matched APC. These data indicate that B7-1 upregulation results from contact between bystander B cells and activated T hybridomas in vitro by CD40-CD40L interaction, without the requirement for TCR/MHC interaction.
Jones
K W
KW
ImmuLogic Pharmaceutical Corporation, Waltham, Massachusetts 02154, USA.
Hackett
C J
CJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D003208:Concanavalin A / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018122:B7-1 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D003208:Concanavalin A; D023201:CD40 Ligand