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氯化汞在布朗 - 挪威大鼠中诱导的自身免疫。I. 单克隆抗体的产生

Autoimmunity induced by HgCl2 in Brown-Norway rats. I. Production of monoclonal antibodies.

作者信息

Hirsch F, Kuhn J, Ventura M, Vial M C, Fournie G, Druet P

出版信息

J Immunol. 1986 May 1;136(9):3272-6.

PMID:3485684
Abstract

Mercuric chloride (HgCl2) induces in Brown-Norway rats (BN) a B cell polyclonal activation resulting in autoimmune disease. Spleen cells from BN rats injected with HgCl2 were fused with IR983F, a nonsecreting rat myeloma cell line, in order to obtain monoclonal antibodies reacting with autoantigens or IgE-producing hybridomas. After screening for immunoglobulin-producing clones, we found 5% clones with anti-tissue activity, 8% with anti-TNP activity, and 41% secreting IgE. Among the anti-tissue monoclonal antibodies, one recognizes both TNP and mesangial structures of rat normal glomeruli, which could be an as yet unrecognized mechanism of nephrotoxicity. These experiments 1) confirm that HgCl2 induces polyclonal activation, 2) show that the mercury model is of interest to obtain monoclonal IgE and various autoantibodies, and 3) suggest a new possible mechanism of antibody-mediated renal injury.

摘要

氯化汞(HgCl2)可诱导棕色挪威大鼠(BN)发生B细胞多克隆激活,进而引发自身免疫性疾病。为了获得能与自身抗原发生反应的单克隆抗体或产生IgE的杂交瘤,将注射了HgCl2的BN大鼠的脾细胞与非分泌型大鼠骨髓瘤细胞系IR983F进行融合。在筛选产生免疫球蛋白的克隆后,我们发现5%的克隆具有抗组织活性,8%具有抗TNP活性,41%分泌IgE。在抗组织单克隆抗体中,有一种既能识别TNP,又能识别大鼠正常肾小球的系膜结构,这可能是一种尚未被认识的肾毒性机制。这些实验:1)证实HgCl2可诱导多克隆激活;2)表明汞模型对于获得单克隆IgE和各种自身抗体具有重要意义;3)提示了抗体介导的肾损伤的一种新的可能机制。

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