Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4+ T-cell proliferation and IFN-γ production in response to myelin basic protein and myelin oligodendrocyte glycoprotein

Christopher T. Harp, Sara Ireland, Laurie S Davis, Gina Remington, Bonnie Cassidy, Petra D. Cravens, Olaf Stuve, Amy E. Lovett-Racke, Todd N. Eagar, Benjamin Greenberg, Michael K. Racke, Lindsay G Cowell, Nitin J. Karandikar, Elliot Frohman, Nancy L Monson

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Recent evidence suggests that B- and T-cell interactions may be paramount in relapsingremitting MS (RRMS) disease pathogenesis. We hypothesized that memory B-cell pools from RRMS patients may specifically harbor a subset of potent neuro-APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and lymphotoxin-α secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4+ T-cell proliferation and IFN-γ secretion in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Notwithstanding the fact that the phenotypic parameters that promote efficient Ag presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4+ T-cell proliferation in response to myelin basic protein and myelin oligodendrocyte glycoprotein was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can activate T cells.

Original languageEnglish (US)
Pages (from-to)2942-2956
Number of pages15
JournalEuropean Journal of Immunology
Volume40
Issue number10
DOIs
StatePublished - Oct 1 2010

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Keywords

  • Ag presentation
  • Autoimmunity
  • B cells
  • MS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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