Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
J Clin Immunol. 2013 Jan;33 Suppl 1(Suppl 1):S50-6. doi: 10.1007/s10875-012-9795-8. Epub 2012 Sep 19.
We have discovered a role for natural autoantibodies in central nervous system repair, remyelination and axon protection. These natural human antibodies are of the immunoglobulin M (IgM) isotype, and they bind to the surface of neural cells. The epitope of the antibody includes sialic acid because treatment with sialidase disrupts the binding. A fully human recombinant form of one of these IgMs, rHIgM12, has the same properties as the serum-derived IgM. rHIgM12 enhanced polarized axonal outgrowth from primary neurons when presented as a substrate in vitro and improved motor functions in chronically Theiler's virus-infected SJL mice, a model of MS. rHIgM12 bound to neuronal surfaces and induced cholesterol and ganglioside (GM1) clustering, indicating that rHIgM12 functions through a mechanism of axonal membrane stabilization. Our work demonstrates that a natural human neuron-binding IgM can regulate membrane domain dynamics. This antibody has the potential to improve neurologic disease.
我们发现天然自身抗体在中枢神经系统修复、髓鞘再生和轴突保护中发挥作用。这些天然的人类抗体属于免疫球蛋白 M（IgM）同种型，它们与神经细胞表面结合。抗体的表位包括唾液酸，因为唾液酸酶的处理会破坏结合。一种此类 IgM 的全人源重组形式，rHIgM12，具有与血清衍生的 IgM 相同的性质。当 rHIgM12 在体外作为基质呈现时，增强了原代神经元的极化轴突生长，并改善了慢性 Theiler 病毒感染 SJL 小鼠（MS 的模型）的运动功能。rHIgM12 与神经元表面结合，并诱导胆固醇和神经节苷脂（GM1）聚集，表明 rHIgM12 通过轴突膜稳定化的机制发挥作用。我们的工作表明，一种天然的人类神经元结合 IgM 可以调节膜域动力学。这种抗体有可能改善神经疾病。
