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H Kimata and A Yoshida
Department of Pediatrics, Kyoto University Hospital, Japan.
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.
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