Dysmyelination induced in vitro by IgM antisulfatide and antigalactocerebroside monoclonal antibodies.
Antiglycolipid antibodies cause a distinctive form of dysmyelination in vivo characterized by marked widening of the myelin period. Such "expanded" or "wide-spaced" myelin occurs in peripheral nerves in certain paraproteinemias and in the CNS in multiple sclerosis. We have used an in vitro system to reproduce this pathology under controlled conditions to assess the role of antibody specificity and class and the need for cofactors in generating this kind of lesion in peripheral myelin. Schwann cell myelin formed in vitro around dorsal root ganglion cell axons was exposed for 3-14 days to hybridoma cells that produce specific monoclonal antibodies. Typical wide-spaced myelin developed after exposure to either O4, which produces an IgM antisulfatide antibody, or O1, which produces an IgM antigalactocerebroside antibody. In both cases, the effect was apparent by three days in paranodal as well as internodal myelin, especially in the outer lamellae. This change did not depend on the presence of complement or macrophages in the cultures. Exposure to anti-GalC hybridoma cells, which produce an IgG3 antiglycolipid antibody, did not produce wide-spaced myelin, nor did exposure to hybridoma cells that secrete IgM antibodies directed against a non-myelin antigen. The location and rapidity of the pathologic changes seen after O4 or O1 are consistent with penetration of the antibodies through the external mesaxon of already formed myelin and then between compact lamellae, progressively spreading them apart in the centripetal direction. This in vitro model shows that either of two specific monoclonal IgM antiglycolipid antibodies can alone reproduce a well known form of myelin pathology under defined conditions.
Rosenbluth
Jack
J
Department of Physiology and Neuroscience, NYU School of Medicine, New York, New York, USA. rosenj03@popmail.med.nyu.edu
Moon
David
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003711:Demyelinating Diseases / Q000276:immunology* / Q000378:metabolism; D005699:Galactosylceramides / Q000276:immunology*; D005727:Ganglia, Spinal; D006825:Hybridomas / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology*; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000737:chemistry / Q000276:immunology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012583:Schwann Cells; D013433:Sulfoglycosphingolipids / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D005699:Galactosylceramides; D007075:Immunoglobulin M; D013433:Sulfoglycosphingolipids