The long term objective of this proposal is to determine the mechanisms involved in the activation of B cells to specific antibody secretion. This proposal stems from a series of studies which have demonstrated that the mitogen induced culture supernatant of the T cell hybridoma FS6-14.13 and the constitutive culture supernatant of the macrophage tumor line P388D1 contain nonspecific factors which will induce normal, resting, murine B cells to increased I-A expression and antigen presenting capacity. Based on these observations the proposed studies will focus on the following objectives. 1. Do the observed effects of the interleukin preparations on cytofluorometric measurements of I-A expression involve the induction of I-A specific mRNA and do these changes extend to increased expression of other B cell surface molecules such as immunoglobulin I-E, and class I K and D molecules? 2. Biochemical purification and/or molecular cloning of the T cell lymphokine responsible for inducing increased B cell Ia expression and correlation of this activity with B cell growth factor as defined in the anti-Ig costimulator assay. 3. Isolation of a monoclonal antibody against the B cell receptor for the Ia inducing lymphokine for characterization of its role in B cell activation. 4. Evaluation of whether the observed effects of the interleukin preparations on Ia expression are involved in the induction of hapten specific antibody responses to soluble protein antigens. The complexity of events which occur during humoral immune responses has become increasingly apparent. With the development of more sophisticated approaches, one might hope to unravel these complexities, to the benefit of both clinical and basic science.
