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

• Published in: Journal of neuropathology and experimental neurology Vol. 70; no. 11; pp. 992 - 1005
• Main Authors: Kap, Yolanda S, Bauer, Jan, Driel, Nikki van, Bleeker, Wim K, Parren, Paul W.H.I, Kooi, Evert-Jan, Geurts, Jeroen J.G, Laman, Jon D, Craigen, Jenny L, Blezer, Erwin, 't Hart, Bert A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.11.2011; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Animals; Antibodies - therapeutic use; Antigens, CD20 - immunology; Antigens, CD20 - metabolism; Ataxia; B-Lymphocytes - drug effects; B-Lymphocytes - pathology; Biological and medical sciences; Brain - metabolism; Brain - pathology; Calgranulin B - metabolism; Callithrix; Complement C9 - metabolism; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - pathology; Freund's Adjuvant - adverse effects; Histocompatibility Antigens Class II - metabolism; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Laboratory animals; Magnetic Resonance Imaging; Medical sciences; Myelin Proteins - adverse effects; Myelin Proteolipid Protein - metabolism; Myelin-Oligodendrocyte Glycoprotein; Nerve Fibers, Myelinated - pathology; Neurofilament Proteins - metabolism; Neurology; NMR; Nuclear magnetic resonance; Nutrition research; Pathology; Proteins; Rodents; Statistics, Nonparametric; Studies; Tetraspanin-29 - metabolism; Traumas. Diseases due to physical agents; Autoimmunity; Immunopathology; Nervous system diseases; Multiple sclerosis; Encephalomyelitis; Callithrix jacchus; Experimental autoimmune encephalomyelitis; Rituximab; Autoimmune disease; Ofatumumab; White matter; Inflammatory disease; Cerebral disorder; B cell; Vertebrata; Anatomic pathology; Mammalia; Depletion; Demyelination; Central nervous system disease; Primates; Simioidea; β Cell; Spinal cord disease
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/NEN.0b013e318234d421

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.