TY - JOUR
T1 - B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis
AU - Harp, Chelsea R.Parker
AU - Archambault, Angela S.
AU - Sim, Julia
AU - Ferris, Stephen T.
AU - Mikesell, Robert J.
AU - Koni, Pandelakis A.
AU - Shimoda, Michiko
AU - Linington, Christopher
AU - Russell, John H.
AU - Wu, Gregory F.
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1402236
DO - 10.4049/jimmunol.1402236
M3 - Article
C2 - 25895531
AN - SCOPUS:84929629444
SN - 0022-1767
VL - 194
SP - 5077
EP - 5084
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -