Differential sialylation of cell surface glycoconjugates in a human B lymphoma cell line regulates susceptibility for CD95 (APO-1/Fas)-mediated apoptosis and for infection by a lymphotropic virus
Differential sialylation of cell surface glycoconjugates in a human B lymphoma cell line regulates susceptibility for CD95 (APO-1/Fas)-mediated apoptosis and for infection by a lymphotropic virus
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DOI：
10.1093/glycob/9.6.557
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发表时间：
1999-06-01
期刊：
影响因子：
4.3
通讯作者：
Pawlita, M
中科院分区：
文献类型：
--
作者：
Keppler, OT;Peter, ME;Pawlita, M
唾液酸作为细胞表面糖复合物上的末端糖残基，在多种生物过程中发挥着重要作用。在这项研究中，我研究了人 B 淋巴瘤细胞系 BJA-B 的亚克隆细胞表面糖缀合物糖基化的差异，并研究了此类差异的功能含义。就大多数测试的 B 细胞相关抗原的表达水平以及寡糖链上倒数第二个糖部分的存在而言，亚克隆在表型上无法区分。然而，亚克隆之间的显着差异在于糖缀合物唾液酸化的总体水平，涉及 α-2,6 和 α-2,3 连接的唾液酸残基。因此，亚克隆被分类为高度唾液酸化（组I）或低唾液酸化（组II）。两种唾液酸依赖性受体介导过程的功能与 BJA-B 亚克隆的唾液酸化状态相关。 B 淋巴嗜乳头空泡病毒 (LPV) 的敏感性和结合取决于宿主细胞的高唾液酸化状态，表明 BJA-B 细胞中的差异唾液酸化可以通过其 α-2,6-唾液酸化糖蛋白受体调节 LPV 感染，由人 CD95 配体或细胞毒性抗 CD95 单克隆抗体诱导的 CD95 介导的细胞凋亡在低唾液酸化的 II 组细胞中显着增强。内源性唾液酸化的增加可能是一种抗凋亡机制，可将肿瘤细胞转化为更恶性的表型。据我们所知，这是第一份证明克隆细胞系中差异唾液酸化可能调节病毒和信号转导受体功能的报告。
Sialic acid, as a terminal saccharide residue on cell surface glycoconjugates, plays an important role in a variety of biological processes. In this study, me investigated subclones of the human B lymphoma cell line BJA-B for differences in the glycosylation of cell surface glycoconjugates, and studied the functional implications of such differences. With respect to the expression level of most of the tested B cell-associated antigens, as well as the presence of penultimate saccharide moieties on oligosaccharide chains, subclones were phenotypically indistinguishable. Marked differences among subclones, however, were found in the overall level of glycoconjugate sialylation, involving both alpha-2,6 and alpha-2,3-linked sialic acid residues. Accordingly, subclones were classified as highly- (group I) or hyposialylated (group II). The function of two sialic acid-dependent receptor-mediated processes is correlated with the sialylation status of BJA-B subclones. Susceptibility to and binding of the B lymphotropic papovavirus (LPV) was dependent on a high sialylation status of host cells, suggesting that differential sialylation in BJA-B cells can modulate LPV infection via its alpha-2,6-sialylated glycoprotein receptor, CD95-mediated apoptosis, induced by either the human CD95 ligand or a cytotoxic anti-CD95 monoclonal antibody, was drastically enhanced in hyposialylated group II cells. An increase in endogenous sialylation may be one anti-apoptotic mechanism that converts tumor cells to a more malignant phenotype, To our knowledge, this is the first report demonstrating that differential sialylation in a clonal cell line may regulate the function of virus and signal-transducing receptors.