Our preliminary studies have demonstrated 1) autocrine stimulation of cells of B lymphocyte lines derived from Burkitt's Lymphoma and transformed in vitro by Epstein-Barr Virus (EBV); 2) production of and response to an Interleukin-1 like factor by the same lines; and 3) acquisition of autostimulatory response by B cells coincident with EBV conversion. We now propose experiments to gain information about the role of growth enhancing factors as autocrines in immortalized B lymphocytes. We plan to compare the identity of the autostimulatory growth factor to IL-1, by means of antibody to IL-1 and a T cell clone responsive to IL-1. If the growth factor is a member of the IL-1 family, we shall determine whether EBV conversion causes B lymphocytes to become responsive to IL-1, whether immortalization can occur in presence of antibody to IL-1, and whether IL-1 bearing cells can stimulate growth in EBV-carrying cells. Regardless of the identity of the growth factor, we shall biochemically purify the stimulatory factor(s) in GE-S and produce antibody to it. B lymphocytes will be studied for both production of and proliferative response to this factor in active EBV infection; cycling B cells will be made quiescent and studied for factor expression; and growth factor responses will be evaluated in activated normal as well as immortalized B lymphocytes. Completion of these studies will illuminate mechanisms underlying controlled cellular proliferation.
