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

• Published in: The Journal of immunology (1950) Vol. 194; no. 11; pp. 5077 - 5084
• Main Authors: Parker Harp, Chelsea R, Archambault, Angela S, Sim, Julia, Ferris, Stephen T, Mikesell, Robert J, Koni, Pandelakis A, Shimoda, Michiko, Linington, Christopher, Russell, John H, Wu, Gregory F
• Format: Journal Article
• Language: English
• Published: United States 01.06.2015
• Subjects: Animals; Antigen Presentation - immunology; B-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - immunology; Dendritic Cells - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - immunology; Mice; Mice, Inbred C57BL; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Myelin-Oligodendrocyte Glycoprotein - administration & dosage; Myelin-Oligodendrocyte Glycoprotein - immunology; Neurogenic Inflammation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1402236

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.