Novel B cell-dependent multiple sclerosis model using extracellular domains of myelin proteolipid protein

Alexander W Boyden; Ashley A Brate; Nitin J Karandikar

doi:10.1038/s41598-020-61928-w

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Novel B cell-dependent multiple sclerosis model using extracellular domains of myelin proteolipid protein

Journal article

Open access

Peer reviewed

Novel B cell-dependent multiple sclerosis model using extracellular domains of myelin proteolipid protein

Alexander W Boyden, Ashley A Brate and Nitin J Karandikar

Scientific reports, Vol.10(1), pp.5011-5011

03/19/2020

DOI: 10.1038/s41598-020-61928-w

PMCID: PMC7081236

PMID: 32193439

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https://doi.org/10.1038/s41598-020-61928-wView

Published (Version of record) Open Access

Abstract

Therapeutic success of B cell-targeting approaches in multiple sclerosis (MS) has intensified research into the pathogenic and regulatory roles these cells play in demyelinating disease. Dissecting the function of B cells in the MS mouse model experimental autoimmune encephalomyelitis (EAE) is largely confined to induction with either the myelin oligodendrocyte glycoprotein epitope MOG or the full-length recombinant human MOG protein, the latter representing the most-used B cell-dependent EAE model. There is a clear need to investigate B cell function in additional myelin antigen contexts. Unlike MOG , where lack of B cells yields more severe disease, we show here that the immunodominant myelin proteolipid protein epitope (PLP ) elicited identical EAE in WT and μMT mice, suggesting an absence of B cell engagement by this peptide. We hypothesized that a longer PLP antigen may better engage B cells and designed a peptide encompassing the extracellular domains (ECD) of PLP. We demonstrate here that PLP -immunized B cell-deficient mice failed to exhibit EAE. In contrast, PLP induced EAE not only in WT mice, but in B cell-sufficient mice incapable of secreting antibodies, suggesting a predominant antigen presentation role. These results establish a novel, efficient B cell-dependent EAE model.

Animals

B-Lymphocytes - immunology

Disease Models, Animal

Encephalomyelitis, Autoimmune, Experimental - immunology

Epitopes

Mice, Inbred C57BL

Multiple Sclerosis - etiology

Multiple Sclerosis - immunology

Myelin Proteolipid Protein - immunology

Myelin-Oligodendrocyte Glycoprotein

Peptide Fragments - immunology

Protein Domains

Details

Title: Subtitle: Novel B cell-dependent multiple sclerosis model using extracellular domains of myelin proteolipid protein
Creators: Alexander W Boyden - University of Iowa
Ashley A Brate - University of Iowa
Nitin J Karandikar - University of Iowa
Resource Type: Journal article
Publication Details: Scientific reports, Vol.10(1), pp.5011-5011
DOI: 10.1038/s41598-020-61928-w
PMID: 32193439
PMCID: PMC7081236
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: R01 AI121567 / NIAID NIH HHS I01 BX003677 / BLRD VA
Language: English
Date published: 03/19/2020
Academic Unit: Pathology
Record Identifier: 9984185172802771

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