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|Title: ||B-Cell Depletion Abrogates T Cell-Mediated Demyelination in an Antibody-Nondependent Common Marmoset Experimental Autoimmune Encephalomyelitis Model|
|Authors: ||Jagessar, S.A.|
Blezer, Erwin L. A.
Laman, Jon D.
't Hart, Bert A.
|Issue Date: ||2012|
|Publisher: ||LIPPINCOTT WILLIAMS & WILKINS|
|Citation: ||JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 71 (8), p. 716-728|
|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.|
|Notes: ||[Jagessar, S. Anwar; Heijmans, Nicole; 't Hart, Bert A.] Biomed Primate Res Ctr, Dept Immunobiol, NL-2280 GH Rijswijk, Netherlands. [Bauer, Jan] Med Univ Vienna, Dept Neuroimmunol, Ctr Brain Res, Vienna, Austria. [Blezer, Erwin L. A.] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands. [Laman, Jon D.] Univ Med Ctr, Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Hellings, Niels] Hasselt Univ, Biomed Res Inst, Diepenbeek, Belgium. ['t Hart, Bert A.] Univ Med Ctr Groningen, Dept Med Physiol, NL-9713 AV Groningen, Netherlands.
|ISI #: ||000306974700005|
|Type: ||Journal Contribution|
|Validation: ||ecoom, 2013|
|Appears in Collections: ||Research publications|
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