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

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Beatrix Ueberheide  

PROVIDER: MSV000086842 | MassIVE | Thu Feb 11 10:22:00 GMT 2021

REPOSITORIES: MassIVE