Expression of glycolipid receptors to Shiga-like toxin on human B lymphocytes: a mechanism for the failure of long-lived antibody response to dysenteric disease.
Expression of glycolipid receptors to Shiga-like toxin on human B lymphocytes: a mechanism for the failure of long-lived antibody response to dysenteric disease.
复制标题
人 B 淋巴细胞上志贺样毒素糖脂受体的表达：对痢疾疾病的长效抗体反应失败的机制。
作者：
Amos Cohen;Vicente Madrid;Z. Estrov;Melvin H. Freedman;C. A. Lingwood;Hans
新鲜和转化的人类 B 谱系细胞被发现对志贺样毒素 (SLT)（一种细菌细胞毒素）的细胞毒作用敏感。该毒素与敏感细胞表面表达的糖脂球三糖神经酰胺和半乳糖神经酰胺特异性结合。选择抗 SLT 细胞毒性的突变 Daudi 细胞 (SLTR20) 缺乏 SLT 结合糖脂，并且无法将 SLT 结合到其表面，这表明这些糖脂在介导 SLT 细胞毒性中发挥作用。在筛选 SLT 敏感性的许多正常和转化的淋巴和骨髓细胞中，只有 B 淋巴细胞对 SLT 作用敏感。此外，B淋巴样细胞是唯一表达SLT结合糖脂的细胞。使用 Epstein-Barr 病毒和美洲商陆有丝分裂原进行的体外 B 细胞激活研究均表明，绝大多数 SLT 敏感 B 细胞属于 IgG 和 IgA 定型亚群，而大多数 IgM 和 IgM/D 产生细胞对 SLT 毒性具有抵抗力。选择性消除 IgG 和 IgA 定型细胞可能可以解释志贺氏菌感染的人类中仅产生 IgM 类抗 SLT 抗体，从而导致对痢疾疾病的长期免疫失败。
Fresh and transformed human B lineage cells were found to be sensitive to the cytotoxic action of Shiga-like toxin (SLT), a bacterial cytotoxin. The toxin was specifically bound by the glycolipids globotriosylceramide and galabiosylceramide expressed on the surface of sensitive cells. Mutant Daudi cells selected for resistance to SLT cytotoxicity (SLTR20) were deficient in SLT-binding glycolipids and failed to bind SLT to their surface, suggesting a role for these glycolipids in the mediation of SLT cytotoxicity. Of a number of normal and transformed lymphoid and myeloid cells screened for SLT sensitivity, only B lymphoid cells were susceptible to SLT action. Moreover, B lymphoid cells were the only cells expressing the SLT binding glycolipids. In vitro B cell activation studies with Epstein-Barr virus and pokeweed mitogen both indicated that the vast majority of SLT-sensitive B cells belong to the IgG and IgA committed subset, whereas most IgM and IgM/D producing cells were resistant to SLT toxicity. The selective elimination of IgG and IgA committed cells may explain the production of only IgM class anti-SLT antibodies in Shigella-infected humans leading to the failure of long-term immunity to dysenteric disease.