title: Critical role of activation induced cytidine deaminase in experimental autoimmune encephalomyelitis.
abstract: Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE.
authors.affiliation: Department of Immunology, Genentech Inc., San Francisco, CA 94080, USA.
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Sun
authors.forename: Ivan
authors.initials: I
authors.lastname: Peng
authors.forename: Kate
authors.initials: K
authors.lastname: Senger
authors.forename: Kajal
authors.initials: K
authors.lastname: Hamidzadeh
authors.forename: Mike
authors.initials: M
authors.lastname: Reichelt
authors.forename: Miriam
authors.initials: M
authors.lastname: Baca
authors.forename: Ronald
authors.initials: R
authors.lastname: Yeh
authors.forename: Maria N
authors.initials: MN
authors.lastname: Lorenzo
authors.forename: Andrew
authors.initials: A
authors.lastname: Sebrell
authors.forename: Christopher
authors.initials: C
authors.lastname: Dela Cruz
authors.forename: Lucinda
authors.initials: L
authors.lastname: Tam
authors.forename: Racquel
authors.initials: R
authors.lastname: Corpuz
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Sai
authors.forename: Merone
authors.initials: M
authors.lastname: Roose-Girma
authors.forename: Søren
authors.initials: S
authors.lastname: Warming
authors.forename: Mercedesz
authors.initials: M
authors.lastname: Balazs
authors.forename: Lino C
authors.initials: LC
authors.lastname: Gonzalez
authors.forename: Patrick
authors.initials: P
authors.lastname: Caplazi
authors.forename: Flavius
authors.initials: F
authors.lastname: Martin
authors.forename: Jason
authors.initials: J
authors.lastname: Devoss
authors.forename: Ali A
authors.initials: AA
authors.lastname: Zarrin
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics*; D023061:Gene Order; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D063308:Myelin-Oligodendrocyte Glycoprotein; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase