Skip Navigation LinksHome > November 2011 - Volume 70 - Issue 11 > B-Cell Depletion Attenuates White and Gray Matter Pathology...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e318234d421
Original Articles

B-Cell Depletion Attenuates White and Gray Matter Pathology in Marmoset Experimental Autoimmune Encephalomyelitis

Kap, Yolanda S. PhD; Bauer, Jan PhD; Driel, Nikki van BSc; Bleeker, Wim K. MD, PhD; Parren, Paul W.H.I. PhD; Kooi, Evert-Jan MSc; Geurts, Jeroen J.G. PhD; Laman, Jon D. PhD; Craigen, Jenny L. PhD; Blezer, Erwin PhD; 't Hart, Bert A. PhD

Supplemental Author Material
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Abstract

This study investigated the effect of CD20-positive B-cell depletion on central nervous system (CNS) white and gray matter pathology in experimental autoimmune encephalomyelitis in common marmosets, a relevant preclinical model of multiple sclerosis. Experimental autoimmune encephalomyelitis was induced in 14 marmosets by immunization with recombinant human myelin oligodendrocyte glycoprotein in complete Freund adjuvant. At 21 days after immunization, B-cell depletion was achieved by weekly intravenous injections of HuMab 7D8, a human-anti-human CD20 antibody that cross-reacts with marmoset CD20. In vivo magnetic resonance imaging showed widespread brain white matter demyelination in control marmosets that was absent in CD20 antibody-treated marmosets. High-contrast postmortem magnetic resonance imaging showed white matter lesions in 4of the 7 antibody-treated marmosets, but these were significantly smaller than those in controls. The same technique revealed gray matter lesions in 5 control marmosets, but none in antibody-treated marmosets. Histologic analysis confirmed that inflammation, demyelination, and axonal damage were substantially reduced in brain, spinal cord, and optic nerves of CD20 antibody-treated marmosets. In conclusion, CD20-postive B-cell depletion by HuMab 7D8 profoundly reduced the development of both white and gray matter lesions in the marmoset CNS. These data underline the central role of B cells in CNS inflammatory-demyelinating disease.

© 2011 American Association of Neuropathologists, Inc

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