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

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 CdCl₂ and HgCl₂ on the biology of murine B-lymphocytes were studied. It was shown that CdCl₂ aand HgCl₂ inhibited B-cell RNA and DNA synthesis. The IC₅₀ (the concentration required to inhibit a specific B-cell function by 50%) for CdCl₂ was 30 μM for RNA synthesis and DNA synthesis. The IC₅₀ for HgCl₂ 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 CdCl₂ and HgCl₂. The inhibitory effects exerted by CdCl₂ were rapid, inhibiting RNA synthesis within 2 h of activation. Differentiation to Ig secretion was inhibited by CdCl₂ and HgCl₂ in culture and there appeared to be selective effects on specific Ig isotypes. IgG₃ production was most sensitive to inhibition by CdCl₂ and HgCl₂ followed by IgG₁ 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 CdCl₂. LPS-induced increases in class II MHC expression was inhibited by CdCl₂, as was the constitutive expression of class I MHC antigen. A summary of the IC₅₀ for CdCl₂ are presented. In summary, both CdCl₂ and HgCl₂ 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.