Wheatley L M, Urso D, Tumas K, Maltzman J, Loh E, Levinson A I
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
J Immunol. 1992 May 15;148(10):3105-9.
The presence and structure of nicotinic acetylcholine receptor (nAChR) in the thymus has been a subject of interest for many years because of its possible role in the pathogenesis of the autoimmune disease myasthenia gravis. Using the polymerase chain reaction with primers specific for the alpha-chain of nAChR (nAChR-alpha), an 880-bp homologous band was found after amplification of cDNA prepared from mouse thymus, thymic medullary and cortical epithelial cell lines, but not from thymocytes or kidney. Sequencing of the polymerase chain reaction product from the thymus and thymic medullary and cortical epithelial lines showed identity with skeletal muscle nAChR-alpha over the region examined. This region includes the domains of the molecule on which B cell and T cell autoantigenic targets have been described. No evidence was found in mouse tissue for the exon 3A, which has been described in human muscle and the human rhabdomyosarcoma cell line TE671. Our results provide evidence at the RNA level for the expression of the nAChR-alpha on stromal cells but not on thymocytes in normal murine thymus and are consistent with a role for intrathymic autoantigen expression in the pathogenesis of myasthenia gravis.
多年来,由于烟碱型乙酰胆碱受体(nAChR)在自身免疫性疾病重症肌无力发病机制中可能发挥的作用,其在胸腺中的存在及结构一直是人们关注的焦点。使用针对nAChRα链的特异性引物进行聚合酶链反应,从小鼠胸腺、胸腺髓质和皮质上皮细胞系制备的cDNA扩增后发现了一条880 bp的同源条带,但从胸腺细胞或肾脏中未发现该条带。对来自胸腺、胸腺髓质和皮质上皮系的聚合酶链反应产物进行测序,结果显示在所检测区域与骨骼肌nAChRα相同。该区域包括已描述的B细胞和T细胞自身抗原靶点所在的分子结构域。在小鼠组织中未发现人类肌肉和人类横纹肌肉瘤细胞系TE671中所描述的外显子3A。我们的结果在RNA水平上为正常小鼠胸腺中基质细胞而非胸腺细胞表达nAChRα提供了证据,这与胸腺内自身抗原表达在重症肌无力发病机制中的作用相一致。