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Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies
Author(s) -
von Büdingen HansChristian,
Harrer Melanie D.,
Kuenzle Sandra,
Meier Mirjam,
Goebels Norbert
Publication year - 2008
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200737784
Subject(s) - multiple sclerosis , cerebrospinal fluid , antigen , myelin , epitope , antibody , biology , pathology , monoclonal antibody , immunofluorescence , white matter , immunology , microbiology and biotechnology , central nervous system , medicine , radiology , neuroscience , magnetic resonance imaging
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.