Parker Harp, C. R., Archambault, A. S., Sim, J., Ferris, S. T., Mikesell, R. J., Koni, P. A., Shimoda, M., Linington, C. , Russell, J. H. and 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), pp. 5077-5084. (doi: 10.4049/jimmunol.1402236) (PMID:25895531) (PMCID:PMC4433779)
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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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Linington, Professor Christopher |
Authors: | Parker Harp, C. R., Archambault, A. S., Sim, J., Ferris, S. T., Mikesell, R. J., Koni, P. A., Shimoda, M., Linington, C., Russell, J. H., and Wu, G. F. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Immunology |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
ISSN (Online): | 1550-6606 |
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