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Antibody-mediated CNS demyelination: focal spinal cord lesions induced by implantation of an IgM anti-galactocerebroside-secreting hybridoma

  • Published:
Journal of Neurocytology

Abstract

O1 hybridoma cells, which secrete an IgM antigalactocerebroside, were implanted into the spinal cord of cyclosporine-treated juvenile or adult rats, and the animals were sacrificed ∼2–3 wk later. About half the recipient animals developed myelin lesions. In some, sharply circumscribed foci of demyelination formed within the dorsal columns. Cellular reaction consisted of macrophages containing refractile globules in the parenchyma and within enlarged perivascular spaces as well as thickened endothelial cells. “Shadow plaques” also developed, i.e. regions in which axons were surrounded by thin myelin sheaths, compatible with remyelination. In addition, we found damaged axons, some of which were swollen with organelles, comparable to the enlarged axon profiles seen at sites of constriction or interruption. Compromise of the blood-brain barrier at sites of hybridoma growth was demonstrated by extravasation of Evans blue dye. Discontinuation of cyclosporine was followed by an anti-hybridoma, complement-fixing antibody response within 2–3 d. This model of focal CNS demyelination and remyelination, with evidence of some axon damage, is mediated by a defined IgM antiglycolipid monoclonal antibody secreted within the spinal cord parenchyma. The lesions, which are similar to those of multiple sclerosis, probably result from the interaction between the intrathecally secreted IgM antibody and complement entering from the circulation at foci of compromised blood-brain barrier plus activation of endogenous or hematogenous macrophages via their complement receptors.

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  1. Department of Physiology and Neuroscience, and Rusk Institute, N.Y.U. School of Medicine, New York, NY, 10016, USA

    Jack Rosenbluth, Rolf Schiff, Wei-Lan Liang, Wen-Kai Dou & David Moon

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  1. Jack Rosenbluth
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Rosenbluth, J., Schiff, R., Liang, WL. et al. Antibody-mediated CNS demyelination: focal spinal cord lesions induced by implantation of an IgM anti-galactocerebroside-secreting hybridoma. J Neurocytol 28, 397–416 (1999). https://doi.org/10.1023/A:1007021916210

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