Departments of Neurology and Immunology, Mayo Clinic, College of Medicine, 200 First Street, S.W., Rochester, MN 55905, USA.
Expert Rev Neurother. 2013 Sep;13(9):1017-29. doi: 10.1586/14737175.2013.835601.
Immunoglobulins with germline sequences occur in invertebrates and vertebrates and are named naturally occurring autoantibodies (NAbs). NAbs may target foreign antigens, self- or altered self-components and are part of the normal immunoglobulin repertoire. Accumulating evidence indicates that naturally occurring antibodies can act as systemic surveillance molecules, which tag, damaged or stressed cells, invading pathogens and toxic cellular debris for elimination by the immune system. In addition to acting as detecting molecules, certain types of NAbs actively signal in different cell types with a broad range of responses from induction of apoptosis in cancer cells to stimulation of remyelination in glial cells. This review emphasizes functions and characteristics of NAbs with focus on remyelination-promoting mouse and human antibodies. Human remyelination-promoting NAbs are potential therapeutics to combat a wide spectrum of disease processes including demyelinating diseases like multiple sclerosis. We will highlight the identified glycosphingolipid (SL) antigens of polyreactive remyelination-promoting antibodies and their proposed mechanism(s) of action. The nature of the identified antigens suggests a lipid raft-based mechanism for remyelination-promoting antibodies with SLs as most essential raft components. However, accumulating evidence also suggests involvement of other antigens in stimulation of remyelination, which will be discussed in the text.
具有胚系序列的免疫球蛋白存在于无脊椎动物和脊椎动物中，被命名为天然自身抗体（NAbs）。NAbs 可能针对外来抗原、自身或改变的自身成分，是正常免疫球蛋白库的一部分。越来越多的证据表明，天然存在的抗体可以作为系统监测分子，标记受损或应激细胞、入侵病原体和毒性细胞碎片，以便免疫系统清除。除了作为检测分子外，某些类型的 NAbs 还可以在不同类型的细胞中主动发出信号，引发广泛的反应，从诱导癌细胞凋亡到刺激神经胶质细胞髓鞘再生。本文重点介绍 NAbs 的功能和特性，特别是促进髓鞘再生的鼠源和人源抗体。人类促进髓鞘再生的 NAbs 是对抗广泛疾病过程的潜在治疗药物，包括多发性硬化症等脱髓鞘疾病。我们将重点介绍鉴定出的多反应性促进髓鞘再生抗体的糖脂（SL）抗原及其作用机制。鉴定出的抗原性质表明，SL 作为最基本的筏成分，基于脂筏的机制是促进髓鞘再生的抗体。然而，越来越多的证据也表明其他抗原参与了髓鞘再生的刺激，本文将对此进行讨论。
