Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination

Abstract

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.

Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels

“…The most efficient treatment modality for neurodegeneration remains an early and aggressive anti-inflammatory intervention, because the prevention of tissue injury may best control the escalating T-cell-driven and bystander B-cell activation, ongoing breakdown of blood-brain barrier (BBB) and epitope spreading, that may perpetuate neuroaxonal damage [4]. After the impressive efficacy of anti-CD20 antibody therapy for patients with a relapsing-remitting form of the disease, there is renewed attention to B cells in the pathogenesis of MS [5]. Recent research highlights the central role of B lymphocytes in the development of MS lesions, in particular the main role of IgG and IgM in newly forming lesions [6].…”