B-Cell Depletion Abrogates T Cell-Mediated Demyelination in an Antibody-Nondependent Common Marmoset Experimental Autoimmune Encephalomyelitis Model

S. Anwar Jagessar, Nicole Heijmans, Jan Bauer, Erwin L. A. Blezer, Jon D. Laman, Niels Hellings, Bert A. 't Hart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)

Abstract

CD20-positive B-cell depletion is a highly promising treatment for multiple sclerosis (MS), but the mechanisms underlying therapeutic effects are poorly understood. B cells are thought to contribute to MS pathogenesis by producing autoantibodies that amplify demyelination via opsonization of myelin. To analyze autoantibody-nondependent functions of B cells in an animal model of MS, we used a novel T cell-driven experimental autoimmune encephalomyelitis (EAE) model in marmoset monkeys (Callithrix jacchus). In this model, demyelination of brain and spinal cord white and gray matter and the ensuing neurological deficits are induced by immunization with peptide 34 to 56 of myelin/oligodendrocyte glycoprotein (MOG(34) (56)) in incomplete Freund's adjuvant. Although autoantibodies do not have a detectable pathogenic contribution in the model, depletion of B cells with monoclonal antibody 7D8, a human IgG1 kappa monoclonal antibody against human CD20, suppressed clinical and pathological EAE. In B cell-depleted monkeys, the activation of peptide-specific Th17-producing and cytotoxic T cells, which in previous studies were found to play an essential role in disease induction, was impaired. Thus, we demonstrate a critical antibody-nondependent role for B cells in EAE, that is, the activation of pathogenic T cells.

Original languageEnglish
Pages (from-to)716-728
Number of pages13
JournalJournal of neuropathology and experimental neurology
Volume71
Issue number8
DOIs
Publication statusPublished - Aug-2012

Keywords

  • B-cell depletion
  • CD20
  • Experimental autoimmune encephalomyelitis
  • Marmoset
  • Multiple sclerosis
  • Neuroimmunology
  • T cell
  • MYELIN OLIGODENDROCYTE GLYCOPROTEIN
  • WHITE-MATTER LESIONS
  • MULTIPLE-SCLEROSIS
  • MONOCLONAL-ANTIBODY
  • CALLITHRIX-JACCHUS
  • MAGNETIC-RESONANCE
  • PRIMATE MODEL
  • PROGRESSION
  • BRAIN
  • ACTIVATION

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