Immunoglobulin transgenes in B lymphocyte development, tolerance, and autoimmunity.
Immunoglobulin transgenes in B lymphocyte development, tolerance, and autoimmunity.
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DOI：
10.1159/000060494
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
D. Melamed;D. Nemazee
中科院分区：
文献类型：
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作者：
D. Melamed;D. Nemazee
B淋巴细胞生成是由细胞接触和生长因子介导的细胞内和细胞外机制调节的严格控制的过程。这一过程已经发展到消除自身反应性B细胞，从而维持生物体的完整性。相比之下，非自身反应性B细胞被选择进入长寿命的外周B细胞库，并且可以参与宿主防御免疫应答。在极少数情况下，自身反应性B细胞存活于外周，并可被触发分泌自身抗体并参与自身免疫性疾病。虽然B细胞在许多自身免疫性疾病中起重要的效应子作用，但尚不清楚B细胞耐受性的缺陷是否引发疾病。为了更好地研究B细胞的发育和耐受机制，产生了免疫球蛋白（IG）转基因（Tg）小鼠，有效地克服了正常小鼠中B细胞的多克隆性，产生了所谓的“单克隆小鼠”。这些小鼠已被广泛用于研究B细胞的发育和免疫耐受性。在此，我们描述了IG基因重排的事件和重要的检查点，在B细胞发育从早期复发或口腔癌细胞，并讨论了连接的Ig-Tg小鼠对这些过程的理解。我们还讨论了产生的免疫球蛋白-转基因小鼠携带疾病相关的自身抗体基因和使用这些小鼠的特点自我/非自我歧视B细胞。
B lymphopoiesis is a tightly controlled process regulated by both intra-and extracellular mechanisms mediated by cell contact and growth factors. This process has evolved to eliminate self-reactive B cells, allowing maintenance of the integrity of the organism. Nonautoreactive B cells, by contrast, are selected into the long-lived peripheral B cell pool and can participate in host defense immune responses. On rare occasions, self-reactive B cells survive in the periphery and can be triggered to secrete autoantibodies and to participate in autoimmune disease. Although B cells play an important effector role in many autoimmune diseases, it is not clear if a defect in B cell tolerance initiates disease. To better study the development and tolerance mechanisms of B cells, immunoglobulin (Ig)-transgenic (Tg) mice were generated, effectively overcoming the polyclonality of B cells in the normal mouse and generating so-called ‘monoclonal mice’. These mice have been used extensively to study development and immune tolerance in B cells. Here we describe Ig gene rearrangement events and important checkpoints in Bcelldevelopmentfromearlyprecursorstomaturecellsanddiscussthecontribution of Ig-Tg mice to the understanding of these processes. We also discuss the generation of Ig-Tg mice bearing disease-associated autoantibody genes and the use of these mice to characterize self/nonself discrimination in B cells.