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Eur J Immunol. 2008 Jul;38(7):2014-23. doi: 10.1002/eji.200737784.

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin-specific antibodies.

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1
Clinical Neuroimmunology Unit, Department of Neurology, University Hospital Zürich, Zürich, Switzerland.

Erratum in

  • Eur J Immunol. 2008 Jul;38(7):2046-7.

Abstract

Clonally expanded plasma cells (cePC) and their presumed products, oligoclonal immunoglobulin G bands (OCB), are characteristic findings in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). While cePC and OCB strongly suggest an involvement of B cell-dependent immune mechanisms in the pathogenesis of MS, their actual pathological relevance and target antigens remain unknown. To further understand the potential role played by cePC, we generated a panel of monoclonal antibodies (MS-mAb) from CSF-derived cePC from four patients with early or definite MS. Single-cell RT-PCR of correctly paired heavy and light chain immunoglobulin genes from individual cePC ensured the subsequent resurrection of their original antigen specificity. Immunofluorescence stainings of MS lesion tissue with MS-mAb revealed myelin reactivity in the cePC repertoire of all four patients and intracellular filament reactivity in one patient. While myelin staining by MS-mAb was only rarely detectable in non-MS CNS white matter tissue, it was greatly enhanced at the edge of demyelinating lesions in MS brain tissue. Our findings provide conclusive evidence for the presence of an antigen-driven B cell response in the CSF of MS patients directed against epitopes present in areas of myelin degradation.

PMID:
18521957
DOI:
10.1002/eji.200737784
[Indexed for MEDLINE]
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