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

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 MOG35-55 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 MOG35-55, where lack of B cells yields more severe disease, we show here that the immunodominant myelin proteolipid protein epitope (PLP178-191) 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 PLPECD-immunized B cell-deficient mice failed to exhibit EAE. In contrast, PLPECD 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.

• Authors: Alexander W Boyden, Ashley A Brate, Nitin J Karandikar
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 5011 (03 19 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32193439 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Epitopes
• Mog protein, mouse
• Myelin Proteolipid Protein
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments
• myelin proteolipid protein (178-191)

Topics

• Animals
• B-Lymphocytes (immunology)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Epitopes
• Mice, Inbred C57BL
• Multiple Sclerosis (etiology, immunology)
• Myelin Proteolipid Protein (immunology)
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments (immunology)
• Protein Domains