Lead stimulates lymphocyte proliferation through enhanced T cell-B cell interaction

We have studied the in vitro effects of lead (Pb) as Pb-acetate (0.1-1000 p pm) on the activation of rat spleen (SP) cells. At a concentration of 0.5 t o 200 ppm, Pb augmented the uptake of [H-3]thymidine, progression of SP cel ls through the cell cycle, and allogeneic and syngeneic mixed lymphocyte re actions. However, at concentrations above 200 ppm, Pb inhibited the prolife ration of these cells. To understand the cellular and molecular basis of th ese responses, we examined the effects of Pb on the proliferation of isolat ed T and/or B cell populations. Pb failed to stimulate the proliferation of isolated T and B cells; however, the addition of gamma-irradiated B cells to T cell cultures or irradiated T cells to B cell cultures resulted in Ph- induced incorporation of [H-3]thymidine. On the other hand, macrophages wer e unable to reconstitute this response. Pb also induced a significant rise in the intracellular concentration of inositol 1,4,5-trisphosphate in SP ce lls; however, unlike the activation of lymphocytes through the antigen rece ptors, Pb did not significantly stimulate protein tyrosine kinase activity. These observations suggest that Pb facilitates the T cell-B cell interacti on-dependent proliferation of lymphocytes through a signaling pathway(s) in dependent of the antigen receptor.