Asakura K, Rodriguez M
Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
Mult Scler. 1998 Jun;4(3):217-21. doi: 10.1177/135245859800400324.
In previous studies we demonstrated that the humoral immune response directed against unique central nervous system (CNS) antigens enhanced CNS remyelination in the Theiler's virus experimental model of multiple sclerosis (MS). To expand on this observation, a mouse IgM kappa monoclonal antibody (mAb) which enhances CNS remyelination, was raised against normal mouse spinal cord homogenate. Characterization of this mAb revealed that it is polyreactive towards variety of intracellular antigens but also reacts to an unidentified surface antigen on oligodendrocytes. The mAb is encoded by germline immunoglobulin genes without somatic mutations consistent with the observation that it is a natural autoantibody. Recently we generated another mouse IgM kappa mAb raised against normal spinal cord homogenate, which also promotes CNS remyelination. Further characterization revealed that both mAbs which promote remyelination have similar binding characteristics. Conventionally Abs which recognize normal CNS components, especially oligodendrocytes or myelin, have been considered to be a disease marker or be involved in the pathogenesis of MS. However, we have identified a unique population of circulating autoantibodies which are beneficial for myelin repair. Therefore this observation indicates the need to reevaluate autoantibody production against myelin components in CSF and blood as markers of disease activity versus repair in MS.
在先前的研究中，我们证明，在多发性硬化症（MS）的泰勒氏病毒实验模型中，针对独特的中枢神经系统（CNS）抗原的体液免疫反应可增强CNS的髓鞘再生。为了进一步拓展这一观察结果，我们制备了一种可增强CNS髓鞘再生的小鼠IgM κ单克隆抗体（mAb），该抗体是针对正常小鼠脊髓匀浆产生的。对该mAb的特性分析表明，它对多种细胞内抗原具有多反应性，但也能与少突胶质细胞上一种未鉴定的表面抗原发生反应。该mAb由种系免疫球蛋白基因编码，无体细胞突变，这与它是一种天然自身抗体的观察结果一致。最近，我们又制备了另一种针对正常脊髓匀浆产生的小鼠IgM κ mAb，它同样能促进CNS的髓鞘再生。进一步的特性分析表明，这两种促进髓鞘再生的mAb具有相似的结合特性。传统上，识别正常CNS成分，尤其是少突胶质细胞或髓磷脂的抗体，被认为是疾病标志物或参与MS的发病机制。然而，我们已经鉴定出了一类独特的循环自身抗体，它们对髓鞘修复有益。因此，这一观察结果表明，有必要重新评估脑脊液和血液中针对髓鞘成分产生的自身抗体，将其作为MS疾病活动与修复的标志物。
