B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis

Chelsea R.Parker Harp, Angela S. Archambault, Julia Sim, Stephen T. Ferris, Robert J. Mikesell, Pandelakis A. Koni, Michiko Shimoda, Christopher Linington, John H. Russell, Gregory F. Wu

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40 Scopus citations

Abstract

B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis, in part as a result of the success of B cell- depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. Although B cell Ag presentation was suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support Ag-specific autoimmune responses by CD4 T cells in EAE is lacking. Using a newly developed murine model of in vivo conditional expression of MHC class II, we reported previously that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the sole APC. In this study, we find that B cells cooperate with dendritic cells to enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive EAE in mice expressing MHCII by B cells alone. These data support a model in which expansion of Ag-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and have the capacity to independently drive neuroinflammation at later stages of disease.

Original languageEnglish (US)
Pages (from-to)5077-5084
Number of pages8
JournalJournal of Immunology
Volume194
Issue number11
DOIs
StatePublished - Jun 1 2015

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Harp, C. R. P., Archambault, A. S., Sim, J., Ferris, S. T., Mikesell, R. J., Koni, P. A., Shimoda, M., Linington, C., Russell, J. H., & Wu, G. F. (2015). B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis. Journal of Immunology, 194(11), 5077-5084. https://doi.org/10.4049/jimmunol.1402236