Immunotoxicology of cadmium and mercury on B-lymphocytes — I. Effects on lymphocyte function

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Heavy metals have been shown to exert immunotoxic effects on humoral immunity. To ascertain the mechanisms by which these immunotoxic effects are exerted, the effects of CdCl 2 and HgCl 2 on the biology of murine B-lymphocytes were studied. It was shown that CdCl 2 aand HgCl 2 inhibited B-cell RNA and DNA synthesis. The IC 50 (the concentration required to inhibit a specific B-cell function by 50%) for CdCl 2 was 30 μM for RNA synthesis and DNA synthesis. The IC 50 for HgCl 2 was 50 and 120 nM for RNA and DNA synthesis, respectively. Cell cycle analysis revealed that B-cells were arrested throughout the cell cycle with CdCl 2 and HgCl 2. The inhibitory effects exerted by CdCl 2 were rapid, inhibiting RNA synthesis within 2 h of activation. Differentiation to Ig secretion was inhibited by CdCl 2 and HgCl 2 in culture and there appeared to be selective effects on specific Ig isotypes. IgG 3 production was most sensitive to inhibition by CdCl 2 and HgCl 2 followed by IgG 1 and IgG 2b and then IgM and IgG 2a. Changes in the expression of B-cell surface antigens induced by LPS were also influenced by CdCl 2. LPS-induced increases in class II MHC expression was inhibited by CdCl 2, as was the constitutive expression of class I MHC antigen. A summary of the IC 50 for CdCl 2 are presented. In summary, both CdCl 2 and HgCl 2 exert early, inhibitory effects on B-cell activation. This is manifested by the inhibition of RNA, DNA and antibody synthesis. However, selective effects on the production of specific Ig isotypes by these metals may influence the ability of B-cells to mount effective immune responses to pathogens.