We are isolating and characterizing lymphokines that activate human B lymphocyte proliferation and differentiation. In order to develop practical assays for such lymphokines, a human (EBV+) B cell line was established that would proliferate in response to B cell growth factor (BCGF) when cultured in less than or equal to 2% serum containing medium. In addition, human peripheral blood B lymphocytes were purified based on their adherence to anti Mu antibody coated culture wells and were used to partially purify a 50 Kd human BCGF. This BCGF was produced by lectin stimulated T lymphoocytes and was free of interleukin 1 and 2 (IL 1 and 2) activities, but could induce B cells to proliferate and to express receptors for IL 2. This presumably accounts for the observed synergistic proliferative effects of mixture of BCGF and IL 2 on B cells. In collaboration with scientists at AFRI we have demonstrated that in vivo administration of recombinant IL 1 beta or IL 1 alpha protects mice against lethal doses of irradiation. This radioprotective effect is seen only when IL 1 is given 20 hrs prior to irradiation. This suggests that the protective effect of IL 1 is indirect, and mediated by one or more of the many effects of IL 1. Mice pretreated with IL 1 do show a partial recovery in the number of nucleated bone marrow cells, whereas there is no such recovery in untreated control mice. The bone marrow cells of IL 1 treated mice 1 wk after lethal irradiation show evidence of increased erythropoesis by colony forming assays (CFU-E). In contrast, administration of several recombinant lymphokines that are induced by IL 1, namely GM-CSF, IL 2 and immune interferon 20 hrs and 3 hrs before irradiation had no protective effect. Thus, these lymphokines do not account for the effects of IL 1. Prostaglandins are also not responsible. The mechanism of IL 1 radioprotection remains to be clarified.
