Kimata H, Yoshida A
Department of Pediatrics, Kyoto University Hospital, Japan.
Blood. 1994 Aug 15;84(4):1193-200.
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.
研究了神经节苷脂对人B细胞反应的影响。在测试的各种神经节苷脂中，只有GM2和GM3抑制IgG亚类和IgM的产生，但不抑制IgA亚类的产生，也不抑制用金黄色葡萄球菌A蛋白（SAC）加白细胞介素-2（IL-2）刺激的人B细胞的胸腺嘧啶核苷摄取。相比之下，GM1、GD1a、GD1b、GD3、GT1b和GQ1b则没有作用。GM2和GM3诱导的抑制作用具有特异性，因为每种都被相应的抗体阻断。在测试的各种细胞因子中，单独的肿瘤坏死因子-α（TNF-α）可抵消GM2和GM3诱导的Ig产生抑制和胸腺嘧啶核苷摄取抑制，而包括IL-1β、IL-3、IL-5、IL-6和干扰素-γ在内的其他细胞因子均未能做到这一点。此外，抗TNF-α抗体而非对照IgG可阻断TNF-α对抑制作用的抵消。GM2和GM3均抑制表面IgG1+（sIgG1+）、sIgG2+、sIgG3+、sIgG4+和sIgM+B细胞的Ig产生、胸腺嘧啶核苷摄取和TNF-α产生，而不影响IL-2与B细胞的结合或TNF-α与B细胞的结合，但对sIgA1+或sIgA2+B细胞没有这种抑制作用。这些发现表明，GM2和GM3通过抑制内源性TNF-α的产生来抑制人sIgG1+、sIgG2+、sIgG3+ sIgG4+和sIgM+B细胞的Ig产生和胸腺嘧啶核苷摄取。
