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 ppm) on the activation of rat spleen (SP) cells. At a concentration of 0.5 to 200 ppm, Pb augmented the uptake of [3H]thymidine, progression of SP cells through the cell cycle, and allogeneic and syngeneic mixed lymphocyte reactions. However, at concentrations above 200 ppm, Pb inhibited the proliferation of these cells. To understand the cellular and molecular basis of these responses, we examined the effects of Pb on the proliferation of isolated 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 Pb-induced incorporation of [3H]thymidine. On the other hand, macrophages were unable to reconstitute this response. Pb also induced a significant rise in the intracellular concentration of inositol 1,4,5-trisphosphate in SP cells; however, unlike the activation of lymphocytes through the antigen receptors, Pb did not significantly stimulate protein tyrosine kinase activity. These observations suggest that Pb facilitates the T cell-B cell interaction-dependent proliferation of lymphocytes through a signaling pathway(s) independent of the antigen receptor.