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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 1/2013

01-01-2013

Therapeutics to Promote CNS Repair: A Natural Human Neuron-Binding IgM Regulates Membrane-Raft Dynamics and Improves Motility in a Mouse Model of Multiple Sclerosis

Authors: Xiaohua Xu, Aleksandar Denic, Arthur E. Warrington, Allan J. Bieber, Moses Rodriguez

Published in: Journal of Clinical Immunology | Special Issue 1/2013

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Abstract

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.
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Metadata
Title
Therapeutics to Promote CNS Repair: A Natural Human Neuron-Binding IgM Regulates Membrane-Raft Dynamics and Improves Motility in a Mouse Model of Multiple Sclerosis
Authors
Xiaohua Xu
Aleksandar Denic
Arthur E. Warrington
Allan J. Bieber
Moses Rodriguez
Publication date
01-01-2013
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue Special Issue 1/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-012-9795-8

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