NDLI: Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid cause demyelination of spinal cord explants

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Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid cause demyelination of spinal cord explants

Content Provider	Semantic Scholar
Author	Blauth, Kevin Soltys, John J. Matschulat, Adeline Reiter, Cory R. Ritchie, Alanna M. Baird, Nicholas L. Bennett, Jeffrey L. Owens, Gregory P.
Copyright Year	2015
Abstract	B cells are implicated in the etiology of multiple sclerosis (MS). Intrathecal IgG synthesis, cerebrospinal fluid (CSF) oligoclonal bands and lesional IgG deposition suggest a role for antibody-mediated pathology. We examined the binding of IgG1 monoclonal recombinant antibodies (rAbs) derived from MS patient CSF expanded B cell clones to central nervous system (CNS) tissue. MS rAbs displaying CNS binding to mouse and human CNS tissue were further tested for their ability to induce complement-mediated tissue injury in ex vivo spinal cord explant cultures. The staining of CNS tissue, primary human astrocytes and human neurons revealed a measurable bias in MS rAb binding to antigens preferentially expressed on astrocytes and neurons. MS rAbs that recognize myelin-enriched antigens were rarely detected. Both myelin-specific and some astrocyte/neuronal-specific MS rAbs caused significant myelin loss and astrocyte activation when applied to spinal cord explant cultures in the presence of complement. Overall, the intrathecal B cell response in multiple sclerosis binds to both glial and neuronal targets and produces demyelination in spinal cord explant cultures implicating intrathecal IgG in MS pathogenesis.
Starting Page	765
Ending Page	781
Page Count	17
File Format	PDF HTM / HTML
DOI	10.1007/s00401-015-1500-6
PubMed reference number	26511623
Journal	Medline
Volume Number	130
Alternate Webpage(s)	http://www.antibodychain.com/printpdf/86892
Alternate Webpage(s)	https://doi.org/10.1007/s00401-015-1500-6
Journal	Acta Neuropathologica
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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