DEOXYSPERGUALIN PREFERENTIALLY INHIBITS THE GROWTH AND MATURATION OF ANTI-CD40-ACTIVATED SURFACE IGD(-LYMPHOCYTES() B)

Deoxyspergualin (DSG), an analogue of spermidin, is a potent immunosup pressive drug with an action quite distinct from that of cyclosporin, rapamycin, or FK506. In this study we investigated the effect of DSG a nd methyldeoxyspergualin (MeDSG) on the proliferation and differentiat ion of human B cells stimulated with anti-CD40 MoAb. Highly purified B cells obtained from tonsillar samples were used as target cells. Both agents inhibited the proliferative response of anti-CD40-stimulated B cells in the absence and presence of IL-4, IL-2 or IL-10 in a dose-de pendent manner. This inhibitory effect differed markedly among cell po pulations based on surface IgD expression: strong inhibition of sIgD() B cells but little inhibition of sIgD(-) B cells. The drugs also sup pressed the production of IgG, IgM and IgA by unfractionated B cells, which suggests that DSG acts against post-switch (sIgD(-)) B cells. Al though the drugs suppressed immunoglobulin synthesis by both sIgD(+) a nd sIgD(-)B cells, the effect was more marked in the sIgD(+) B cells. Analysis of the subclass of IgG secreted by sIgD(+) B cells revealed a decline in IgG1 and IgG3 in the presence of DSG. These results sugges t that DSG preferentially inhibits the growth and maturation of sIgD() naive B cells.