Muryoi T, Kasturi K N, Kafina M J, Saitoh Y, Usuba O, Perlish J S, Fleischmajer R, Bona C A
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
Autoimmunity. 1991;9(2):109-17. doi: 10.3109/08916939109006746.
Tight skin (TSK) mice develop cutaneous hyperplasia accompanied by histopathological alterations of skin and collagen metabolism similar to those described in human scleroderma. Diffuse scleroderma, the most severe form of progressive systemic sclerosis, is associated with the production of autoantibodies specific for Scleroderma 70 antigen (topoisomerase I). Our studies show that there is an increase in the level of serum anti-topoisomerase I (topo I) autoantibodies in aged TSK mice. The monoclonal antibodies isolated from TSK mice bind to epitopes which interact with autoantibodies from scleroderma patients. A significant number of TSK monoclonal anti-topo I antibodies and serum immunoglobulin (Ig) from aged TSK mice bear a cross reactive idiotype (Id) recognized by a syngeneic monoclonal anti-Id antibody obtained from a 2 month-old TSK mouse. Analysis of V gene usage by monoclonal anti-topo I antibodies showed that the majority of these antibodies are encoded by VH genes derived from VHJ558 family pairing with VK genes from various families in a stochastic manner.
紧皮（TSK）小鼠会出现皮肤增生，并伴有与人类硬皮病中所描述的类似的皮肤组织病理学改变和胶原蛋白代谢变化。弥漫性硬皮病是进行性系统性硬化症最严重的形式，与针对硬皮病70抗原（拓扑异构酶I）的自身抗体产生有关。我们的研究表明，老年TSK小鼠血清抗拓扑异构酶I（topo I）自身抗体水平升高。从TSK小鼠中分离出的单克隆抗体与来自硬皮病患者自身抗体相互作用的表位结合。大量来自老年TSK小鼠的TSK单克隆抗topo I抗体和血清免疫球蛋白（Ig）带有一种交叉反应独特型（Id），该独特型可被从2月龄TSK小鼠获得的同基因单克隆抗Id抗体识别。对单克隆抗topo I抗体的V基因使用情况分析表明，这些抗体中的大多数由源自VHJ558家族的VH基因编码，它们以随机方式与来自不同家族的VK基因配对。
