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

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 - Jan 1 2015

Fingerprint

Antigen Presentation
Multiple Sclerosis
B-Lymphocytes
Animal Models
Autoimmune Experimental Encephalomyelitis
Myelin-Oligodendrocyte Glycoprotein
T-Lymphocytes
Autoimmunity
Demyelinating Diseases
Cell- and Tissue-Based Therapy
Dendritic Cells
Immunization
Inflammation

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., ... 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

B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis. / Harp, Chelsea R.Parker; Archambault, Angela S.; Sim, Julia; Ferris, Stephen T.; Mikesell, Robert J.; Koni, Pandelakis A.; Shimoda, Michiko; Linington, Christopher; Russell, John H.; Wu, Gregory F.

In: Journal of Immunology, Vol. 194, No. 11, 01.01.2015, p. 5077-5084.

Research output: Contribution to journalArticle

Harp, CRP, Archambault, AS, Sim, J, Ferris, ST, Mikesell, RJ, Koni, PA, Shimoda, M, Linington, C, Russell, JH & Wu, GF 2015, 'B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis', Journal of Immunology, vol. 194, no. 11, pp. 5077-5084. https://doi.org/10.4049/jimmunol.1402236
Harp, Chelsea R.Parker ; Archambault, Angela S. ; Sim, Julia ; Ferris, Stephen T. ; Mikesell, Robert J. ; Koni, Pandelakis A. ; Shimoda, Michiko ; Linington, Christopher ; Russell, John H. ; Wu, Gregory F. / B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis. In: Journal of Immunology. 2015 ; Vol. 194, No. 11. pp. 5077-5084.
@article{6651664a9ab548c89cb79d95bcda2f1f,
title = "B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis",
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.",
author = "Harp, {Chelsea R.Parker} and Archambault, {Angela S.} and Julia Sim and Ferris, {Stephen T.} and Mikesell, {Robert J.} and Koni, {Pandelakis A.} and Michiko Shimoda and Christopher Linington and Russell, {John H.} and Wu, {Gregory F.}",
year = "2015",
month = "1",
day = "1",
doi = "10.4049/jimmunol.1402236",
language = "English (US)",
volume = "194",
pages = "5077--5084",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

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.

PY - 2015/1/1

Y1 - 2015/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84929629444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929629444&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1402236

DO - 10.4049/jimmunol.1402236

M3 - Article

C2 - 25895531

AN - SCOPUS:84929629444

VL - 194

SP - 5077

EP - 5084

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -