Ganglioside GD1a enhances immunoglobulin production by human peripheral blood mononuclear cells

Objective. We previously reported that ganglioside GD1a greatly enhanced sp ontaneous immunoglobulin (Ig) production by human peripheral blood mononucl ear cells (PBMC) in vitro. We herein examined the mechanism for the stimula tory effect of GD1a. Materials and Methods. PBMC from healthy volunteers were cultured with GD1a . The amounts of IgG, IgM, and IgA and cytokine activity in the culture sup ernatants were measured by enzyme-linked immunosorbent assays. Proliferatio n was determined by [H-3] thymidine uptake. Results. GD1a at 10(-6) M increased IgG, IgM, and IgA production by PBMC 2. 10-fold, 2.10-fold, and 2.23-fold above the control values, respectively. G D1a did not affect the proliferation and viability of PBMC. GD1a did not al ter Ig production of B cells alone. Anti-interleukin-6 (IL-6) or anti-IL-10 antibody each partially blocked the GD1a-induced enhancement of Ig product ion by PBMC, and the addition of both antibodies completely blocked the enh ancement. GD1a increased IL-6 and IL-10 production of monocytes without alt ering those of T cells or B cells. The supernatant from GD1a-treated monocy tes enhanced B cell Ig production to a greater extent than that from medium -treated monocytes, The supernatant-mediated effect of GD1a was partially b locked by anti-IL-6 or anti-IL-10 antibody, and the addition of both antibo dies completely blocked the GD1a effect. GD1a-induced increases of IL-6 and IL-10 production in monocytes were both blocked by Ca2+/calmodulin (CaM)-d ependent phosphodiesterase (PDE) inhibitors, 8-methoxymethyl-3-isobutyl-1-m ethylxanthine and vinpocetin, but not by other signal-transducing enzyme in hibitors. The culture with GD1a enhanced Ca2+/CaM-dependent PDE activity in monocytes. Conclusion. These results suggest that GD1a may indirectly enhance B cell I g production in whole PBMC by increasing IL-6 and IL-10 production of monoc ytes via promoting Ca2+/ CaM-dependent PDE activity. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.