Self-reactive B cells are not eliminated or inactivated by autoantigen expressed on thyroid epithelial cells.
Self-reactive B cells are not eliminated or inactivated by autoantigen expressed on thyroid epithelial cells.
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DOI：
10.1084/jem.186.12.2005
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发表时间：
1997-12-15
期刊：
影响因子：
--
通讯作者：
Goodnow CC
中科院分区：
文献类型：
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作者：
Akkaraju S;Canaan K;Goodnow CC
格雷夫斯病是由甲状腺上皮细胞上产生的针对促甲状腺激素（TSH）受体的自身抗体引起的，并且代表了由与器官特异性细胞膜抗原结合的自身抗体引起的许多自身免疫性疾病的原型。为了研究体液耐受性通常是如何维持器官特异性膜抗原，转基因小鼠产生选择性表达膜结合的鸡蛋溶菌酶（mHEL）的甲状腺上皮。与由系统性mHEL触发的自身反应性B细胞的缺失相反（Hartley，S.B.，克罗斯比河Brink，A.B. Kantor，A.巴斯滕和C.C.再见1991.自然353：765-769），甲状腺细胞上mHEL自身抗原的选择性表达不触发循环的HEL反应性B细胞的消除或失活。这些结果提供的证据表明，在免疫前B细胞库中，对器官特异性抗原的耐受性不是主动获得的，强调了通过其他机制维持对这些抗原的耐受性的重要性。一个完整的内皮屏障隔离器官特异性抗原从循环免疫前B细胞的作用进行了讨论。
Graves' Disease results from the production of autoantibodies against receptors for thyroid stimulating hormone (TSH) on thyroid epithelial cells, and represents the prototype for numerous autoimmune diseases caused by autoantibodies that bind to organ-specific cell membrane antigens. To study how humoral tolerance is normally maintained to organ-specific membrane antigens, transgenic mice were generated selectively expressing membrane-bound hen egg lysozyme (mHEL) on the thyroid epithelium. In contrast to the deletion of autoreactive B cells triggered by systemic mHEL (Hartley, S.B., J. Crosbie, R. Brink, A.B. Kantor, A. Basten, and C.C. Goodnow. 1991. Nature. 353:765–769), selective expression of mHEL autoantigen on thyroid cells did not trigger elimination or inactivation of circulating HEL-reactive B cells. These results provide evidence that tolerance is not actively acquired to organ-specific antigens in the preimmune B cell repertoire, underscoring the importance of maintaining tolerance to such antigens by other mechanisms. The role of an intact endothelial barrier in sequestering organ-specific antigens from circulating preimmune B cells is discussed.