Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin-specific antibodies.
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.
Clinical Neuroimmunology Unit, Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
Hans-Christian
HC
von Büdingen
Melanie D
MD
Harrer
Sandra
S
Kuenzle
Mirjam
M
Meier
Norbert
N
Goebels
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D003106:Colon / Q000276:immunology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies