Ganglioside GT1b suppresses immunoglobulin production by human peripheral blood mononuclear cells

Gangliosides are sialic acid-containing glycolipids and have various immuno modulatory effects. We previously reported that various gangliosides in,vit ro either inhibited or enhanced spontaneous immunoglobulin production by hu man peripheral blood mononuclear cells (PBMC). Among them, GTlb was the mos t inhibitory. In this study, we further examined the mechanism for the inhi bitory effect of CTlb. The inhibitory effect of GTlb was apparent at 0.1 mu M, increased dose dependently, and was maximal at 10 mu M. In the presence of 10 mu M CTlb, spontaneous production of immunoglobulin (Ig)G, IgM and I gA in human PBMC was reduced by 60%, 59.5% and 58%, respectively, compared with controls. GTlb did not affect the proliferation and viability of PBMC, and did not enhance their apoptosis. GTlb did not alter immunoglobulin pro duction of B cells alone. Interleukin (IL)-6 and IL-10 each partially rever sed the GTlb-induced inhibition of immunoglobulin production by PBMC, and t he presence of both cytokines completely reversed the inhibition. GTlb inhi bited IL-6 and IL-IO production in monocytes, without affecting that in T o r B cells. When monocytes were preincubated with GTlb, washed and then cult ured with B and T cells, the immunoglobulin production was also suppressed. These results suggest that GTlb may indirectly suppress immunoglobulin pro duction of B cells in whole PBMC via reducing the production of IL-6 and IL -10 in monocytes. It is thus indicated that GTlb may act as an important in hibitor for human humoral immune responses.