MassIVE MSV000086842

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The B Cell Repertoire in Multiple Sclerosis Reveals Molecular Mimicry between EBNA1 and GlialCAM

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Description

This data set contains the mass spectrometry raw files for the paper The B Cell Repertoire in Multiple Sclerosis Reveals Molecular Mimicry between EBNA1 and GlialCAM. In multiple sclerosis (MS) intrathecal B lymphocytes are directly involved in inflammation and secrete oligoclonal immunoglobulin. However, our understanding of their phenotype, function, and antigen-specificity in MS is incomplete. Molecular mimicry to viruses and self-antigens could be a trigger of autoimmunity. Here we describe phenotypic differences of B cells in blood and cerebro-spinal fluid (CSF) and predominantly implicate plasmablasts in MS pathogenesis. Single-cell paired-chain antibody repertoire sequencing in blood and CSF suggests ongoing intrathecal somatic hypermutation and antigen-specific clonal expansion of intrathecal plasmablasts. The presence of these antibodies was verified using mass spectrometry sequencing of the IgGs isolated from CSF. Selected CSF-derived antibodies were tested against a spectrum of viruses implicated in MS pathogenesis. Antibody MS39p2w174 binds Epstein-Barr Virus (EBV) transcription factor EBNA1 and cross-reacts to the glial cellular adhesion molecule GlialCAM, which is facilitated by serine-phosphorylation. EBNA1 peptide immunization aggravates the mouse model of MS. EBNA1-GlialCAM cross-reactive antibodies are more prevalent in MS patients than in healthy controls. Together, our results suggest that anti-EBNA1- antibodies cross-react with GlialCAM and contribute to MS pathology. This dataset contains the RAW files for the CSF isolated IgGs. [doi:10.25345/C59501] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Multiple Sclerosis ; CSF ; patient IgG

Contact

Principal Investigators:
(in alphabetical order) 		Beatrix Ueberheide, NYU Grossman School of Medicine, USA
Submitting User: Trixi

Publications

Lanz TV, Brewer RC, Ho PP, Moon JS, Jude KM, Fernandez D, Fernandes RA, Gomez AM, Nadj GS, Bartley CM, Schubert RD, Hawes IA, Vazquez SE, Iyer M, Zuchero JB, Teegen B, Dunn JE, Lock CB, Kipp LB, Cotham VC, Ueberheide BM, Aftab BT, Anderson MS, DeRisi JL, Wilson MR, Bashford-Rogers RJM, Platten M, Garcia KC, Steinman L, Robinson WH.
Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM.
Nature. 2022 Mar;603(7900):321-327. Epub 2022 01 24.

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