Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Sci Rep. 2023 Jun 9;13(1):9394. doi: 10.1038/s41598-023-36532-3.
Multiple sclerosis (MS) is an inflammatory demyelinating disease characterized by multiple lesions in the central nervous system. Although the role of B cells in MS pathogenesis has attracted much attention, but the detailed mechanisms remain unclear. To investigate the effects of B cells on demyelination, we analyzed a cuprizone-induced demyelination model, and found that demyelination was significantly exacerbated in B cell-deficient mice. We next investigated whether immunoglobulin affected the myelin formation process using organotypic brain slice cultures and revealed that remyelination was improved in immunoglobulin-treated groups compared with the control group. Analysis of oligodendrocyte-precursor cell (OPC) monocultures showed that immunoglobulins directly affected on OPCs and promoted their differentiation and myelination. Furthermore, OPCs expressed FcγRI and FcγRIII, two receptors that were revealed to mediate the effects of IgG. To the best of our knowledge, this is the first study to demonstrate that B cells act in an inhibitory manner against cuprizone-induced demyelination, while immunoglobulins enhance remyelination following demyelination. Analysis of the culture system revealed that immunoglobulins directly act on OPCs to promote their differentiation and myelination. Future studies to elucidate the effects of immunoglobulins on OPCs in vivo and the detailed mechanisms of these effects may lead to new treatments for demyelinating diseases.
多发性硬化症（MS）是一种以中枢神经系统内多个病灶为特征的炎症性脱髓鞘疾病。虽然 B 细胞在 MS 发病机制中的作用引起了广泛关注，但详细的机制仍不清楚。为了研究 B 细胞对脱髓鞘的影响，我们分析了杯状醇诱导的脱髓鞘模型，发现 B 细胞缺陷小鼠的脱髓鞘明显加重。接下来，我们使用器官型脑片培养物研究了免疫球蛋白是否影响髓鞘形成过程，结果表明与对照组相比，免疫球蛋白处理组的髓鞘再生得到改善。对少突胶质前体细胞（OPC）单细胞培养物的分析表明，免疫球蛋白直接作用于 OPC，并促进其分化和髓鞘形成。此外，OPC 表达 FcγRI 和 FcγRIII，这两种受体介导 IgG 的作用。据我们所知，这是第一项证明 B 细胞在抑制杯状醇诱导的脱髓鞘中起作用，而免疫球蛋白增强脱髓鞘后髓鞘再生的研究。对培养系统的分析表明，免疫球蛋白直接作用于 OPC 以促进其分化和髓鞘形成。未来研究阐明免疫球蛋白对体内 OPC 的影响及其详细作用机制可能为脱髓鞘疾病的治疗提供新方法。
