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.