Lindstrom J M, Engel A G, Seybold M E, Lennon V A, Lambert E H
J Exp Med. 1976 Sep 1;144(3):739-53. doi: 10.1084/jem.144.3.739.
Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.
使用来自用美洲电鳗（电鳗）乙酰胆碱受体（AChR）免疫的大鼠血清中的γ球蛋白组分和纯化的IgG实现了实验性自身免疫性重症肌无力（EAMG）的被动转移。这证明了抗AChR抗体在损害EAMG中神经肌肉传递方面的关键作用。来自慢性EAMG大鼠的抗AChR抗体的被动转移在正常受体大鼠中诱发了EAMG急性期的体征，包括单核炎性细胞侵入运动终板区域。抗体转移后24小时观察到急性EAMG的临床、电生理、组织学和生化体征。受体大鼠出现严重的无力和疲劳，以及EAMG特有的姿势。显著的体重减轻归因于脱水。受体大鼠对运动神经刺激的肌肉反应幅度大幅下降，重复神经刺激诱发特征性递减反应。许多肌纤维中未检测到终板电位，其他肌纤维中微小终板电位的幅度降低。被动转移的EAMG对前臂肌肉的影响比对膈肌的影响更严重，尽管两种肌肉的神经肌肉传递均受损且箭毒敏感性增加。从被动转移EAMG的大鼠肌肉中提取的一些AChR被发现与抗体复合，并且每只大鼠AChR的总产量降低。AChR的定量减少在时间上大致与临床和电生理体征的过程平行。在神经肌肉传递改善时，AChR的量增加到正常水平并超过正常水平。随着血清抗体水平降低，从肌肉中可提取的过量AChR可能代表了因巨噬细胞吞噬突触后膜导致功能性去神经支配而形成的接头外受体。被动转移EAMG所需的抗体量少于结合大鼠肌肉组织中所有AChR分子所需的量。少量抗体的有效性可能通过补体的激活以及吞噬细胞对大面积突触后膜的破坏而放大。在被动转移EAMG的动物中未引发对AChR的自我维持的自身免疫反应。
