Induction of lymphokine responsiveness of hapten-specific B lymphocytes promoted through an antigen-mediated T helper lymphocyte interaction

We describe a new experimental approach designed to detect signals transduced to B cells that have interacted, in an antigen-mediated mechanism, with helper T cells that cannot release soluble mediators. For this purpose, cells from an antigen-specific T helper cell line were treated with cyclosporin A (CSA). The stimulation of CSA-treated T cells with specific antigen in the presence of low concentrations of CSA, demonstrated that the T cells did not release detectable levels of interleukin-2, interleukin-4, and interleukin-5. When such CSA-treated T cells interacted with hapten-specific B cells in the presence of specific antigen, the B cells were found to develop responsiveness to exogenously added growth and differentiation inducing soluble mediators. The development of lymphokine responsiveness in such cultures could be partially blocked by the addition of a monoclonal antibody specific for major histocompatibility complex class II molecules expressed on the B cell surfaces. These results indicated that antigen-mediated interaction between B and T cells, in the absence of lymphokines, resulted in a phenotypic change in B cell behavior and suggested that the signal that promoted this change occurred as a consequence of the T cell antigen receptor binding to B cell surface Ia in association with processed antigen. This experimental system should afford an opportunity to determine the biochemical and molecular consequences in B cells that have interacted, by direct cell contact, with helper T cells.