Inhibition of spontaneous immunoglobulin production by ganglioside GM2 in human B cells.

The effects of gangliosides on spontaneous immunoglobulin (Ig) production in human B cells were studied. Of the various gangliosides tested, including GM1, GM2, GM3, GD1a, GD1b, GD3, GT1b, and GQ1b, only GM2 inhibited Ig production, but not thymidine uptake, in human B cell lines. Moreover, the GM2-induced inhibition was blocked by anti-GM2 mAb, but not by control IgM. Of various cytokines, IL-10 and TNF-alpha each partially counteracted the GM2-induced inhibition, and addition of both IL-10 and TNF-alpha completely counteracted the inhibition. On the other hand, anti-IL-10 mAb plus anti-TNF-alpha mAb inhibited spontaneous Ig production. GM2 inhibited endogenous production of IL-10 and TNF-alpha without affecting the binding of IL-10 and TNF-alpha in B cell lines. GM2 also specifically inhibited spontaneous production of Ig, IL-10, and TNF-alpha in in vivo activated B cells obtained from normal donors. This inhibition was blocked by anti-GM2 mAb and was counteracted specifically by IL-10 plus TNF-alpha. Collectively, GM2 may inhibit spontaneous Ig production by inhibiting endogenous production of IL-10 and TNF-alpha in B cells.