EXPRESSION OF ANTI-DNA IMMUNOGLOBULIN TRANSGENES IN NON-AUTOIMMUNE MICE
EXPRESSION OF ANTI-DNA IMMUNOGLOBULIN TRANSGENES IN NON-AUTOIMMUNE MICE
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DOI：
10.1038/349331a0
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发表时间：
1991-01-24
期刊：
影响因子：
64.8
通讯作者：
WEIGERT, M
中科院分区：
文献类型：
--
作者：
ERIKSON, J;RADIC, MZ;WEIGERT, M
自身反应性B细胞可以通过缺失或失活来调节1。自我耐受性的这些表现在转基因小鼠中表现得非常明显，在转基因小鼠中，自我反应性细胞的数量被人为地扩大了2，3。我们现在扩展了这些模型，以询问对于非疾病相关抗原所描述的B细胞耐受性是否也对自身免疫的靶标起作用。我们选择的目标是DNA。抗DNA抗体是对人类某些自身免疫综合征的诊断，也是系统性自身免疫的小鼠模型--MRI/IPR小鼠的一个特征。针对单链和双链DNA的抗体都与疾病5，6有关。通过建立抗DNA转基因小鼠，我们解决了正常(非自身免疫)小鼠中DNA特异性B细胞是否受到调控的问题。我们确实发现大多数转基因B细胞与DNA结合，但我们未能检测到分泌的抗DNA。我们认为，由于自身反应的结果，这些B细胞在发育过程中受阻。
SELF-REACTIVE B cells can be regulated by either deletion or inactivation 1. These manifestations of self-tolerance have been dramatically shown in transgenic mice in which the number of self-reactive cells has been artificially expanded 2,3. We have now extended these models to ask if B-cell tolerance as described for non-disease-associated antigens also operates for the targets of autoimmunity. The target we have chosen is DNA. Anti-DNA antibodies are diagnostic of certain autoimmune syndromes in humans and are a characteristic of the murine model of systemic autoimmunity, the MRI/Ipr mouse4. Antibodies to both single-stranded and double-stranded DNA have been implicated in disease 5,6. By generating anti-DNA transgenic mice, we have addressed the question of whether DNA-specific B cells are regulated in normal (non-autoimmune) mice. We indeed found that most transgenic B cells bind DNA, yet we failed to detect secreted anti-DNA. We suggest that as a consequence of their self-reactivity these B cells are developmentally arrested.