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.