Inhibition of human B cell activation by gold compounds.
The mechanism of action of gold compounds, which are effective in the treatment of rheumatoid arthritis (RA), has not been clearly identified. Although one of the characteristic features of RA is chronic stimulation of B cells, the effects of gold compounds on B cells have not been precisely assessed. We therefore examined the effects of gold sodium thiomalate (GST) on human B cells. IgM production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SA) plus IL-2. T cell proliferation and IFN-gamma production were induced from highly purified T cells by stimulation with immobilized mAb to CD3. As little as 0.1 microg/ml (0.25 microM) GST almost completely suppressed B cell IgM production, whereas it did not suppress T cell proliferation or IFN-gamma production. The inhibition of IgM production by GST is not due to its thiomalate, but is most likely due to its gold components, since thiomalate alone did not inhibit IgM production. GST was required at the initiation of cultures to exert optimal suppressive effects on IgM production. Moreover, GST suppressed the expression of IL-2R (CD25) and transferrin receptor (CD71) on SA-stimulated B cells. These results indicate that GST preferentially inhibits the function of B cells at concentrations much lower than those which inhibit the function of T cells by interfering with the initial activation of B cells. The direct inhibitory effects of GST on human B cell activation described here may contribute at least in part to its therapeutic effect in RA.
Second Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
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Hirohata
D001172:Arthritis, Rheumatoid / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003864:Depression, Chemical; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
D006052:Gold Sodium Thiomalate