Editing disease-associated autoantibodies
Editing disease-associated autoantibodies
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DOI：
10.1016/s1074-7613(00)80673-1
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发表时间：
1997-01-01
期刊：
影响因子：
32.4
通讯作者：
Weigert, M
中科院分区：
文献类型：
--
作者：
Chen, C;Prak, EL;Weigert, M
我们已经培育出了定点转基因小鼠，其转基因编码抗 DNA 抗体。这些抗体是在自身免疫小鼠模型和人类 SLE 模型中观察到的狼疮相关抗 DNA 的代表，并且具有致病性自身抗体的常见特征。作为非自身免疫小鼠中的常规转基因，抗 DNA B 细胞已被证明被删除或失活。自身反应性 B 细胞还可以通过一种称为受体编辑的过程来逃避负调控。在这里，我们描述了两种组合的免疫球蛋白 H 链和 L 链定点转基因小鼠模型，并表征了它们的编辑表型。一种模型，3H9R/V kappa 4R，具有易于缺失的表型并经过编辑，主要是通过蛙跳事件使轻链失活。在另一种模型 3H9R/V kappa 8R 中，B 细胞对无反应性敏感并维持其大部分 HR 和 LR 链。这些研究阐明了编辑与其他耐受机制之间的关系。
We have generated site-directed transgenic mice whose transgenes code for anti-DNA antibodies. These antibodies are representative of the lupus-associated anti-DNAs seen in mouse models of autoimmunity and human SLE, and have the usual characteristics of pathogenic autoantibodies. As conventional transgenics in nonautoimmune mice, anti-DNA B cells have been shown to be deleted or inactivated. Autoreactive B cells can also escape negative regulation by a process called receptor editing. Here we describe two combined immunoglobulin H and L chain site-directed transgenic mouse models and characterize their editing phenotypes. One model, 3H9R/V kappa 4R, has a deletion-prone phenotype and undergoes editing, primarily by inactivation of the light chain by leap-frogging events. In the other model, 3H9R/V kappa 8R, B cells are susceptible to anergy and maintain most of their HR and LR chains. These studies clarify the relationship between editing and other mechanisms of tolerance.