Differential effects of gangliosides on Ig production and proliferation by human B cells.
The effects of gangliosides on human B-cell responses were studied. Of various gangliosides tested, only GM2 and GM3 inhibited production of IgG subclasses and IgM, but not IgA subclasses, and thymidine uptake by human B cells stimulated with SAC plus interleukin-2 (IL-2). In contrast, GM1, GD1a, GD1b, GD3, GT1b, and GQ1b were without effects. GM2- and GM3-induced inhibition were specific, because each was blocked by a corresponding antibody. Of various cytokines tested, tumor necrosis factor-alpha (TNF-alpha) alone counteracted GM2- and GM3-induced inhibitions of Ig production and thymidine uptake, whereas other cytokines including IL-1 beta, IL-3, IL-5, IL-6, and interferon-gamma each failed to do so. Moreover, anti-TNF-alpha antibody, but not control IgG, blocked the counteraction of inhibition by TNF-alpha. GM2 and GM3 each inhibited Ig production, thymidine uptake, and TNF-alpha production by surface IgG1+ (slG1+), sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells without affecting IL-2 binding or TNF-alpha binding to B cells, but had no such inhibitory effects on sIgA1+ or sIgA2+ B cells. These findings indicate that GM2 and GM3 inhibit Ig production and thymidine uptake by human sIgG1+, sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells by inhibiting endogenous TNF-alpha production.
Kimata
H
H
Department of Pediatrics, Kyoto University Hospital, Japan.
Yoshida
A
A
D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005732:Gangliosides / Q000494:pharmacology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000145:classification; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000145:classification; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D014066:Palatine Tonsil; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D005732:Gangliosides; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016898:Interferon-alpha; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA