title: Secondary B cell receptor diversification is necessary for T cell mediated neuro-inflammation during experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  Clinical studies of B cell depletion in Multiple Sclerosis (MS) have revealed that B Lymphocytes are involved in the neuro-inflammatory process, yet it remains unclear how B cells can exert pro- and anti-inflammatory functions during MS. Experimental Autoimmune Encephalomyelitis (EAE) is an animal model of MS whereby myelin-specific T cells become activated and subsequently migrate to the Central Nervous System (CNS) where they perform pro-inflammatory functions such as cytokine secretion. Typically EAE is induced by immunization of mice of a susceptible genetic background with peptide antigen emulsified in Complete Freund's Adjuvant. However, novel roles for B-lymphocytes in EAE may also be explored by immunization with full-length myelin oligodendrocyte glycoprotein (MOG) that contains the B cell conformational epitope. Here we show that full length MOG immunization promotes a chronic disease in mice that depends on antigen-driven secondary diversification of the B cell receptor.
  
  
  METHODS
  Activation-Induced Deaminase (AID) is an enzyme that is essential for antigen-driven secondary diversification of the B cell receptor. We immunized AID(-/-) mice with the extracellular domain (amino acids 1-120) of recombinant human MOG protein (rhMOG) and examined the incidence and severity of disease in AID(-/-) versus wild type mice. Corresponding with these clinical measurements, we also evaluated parameters of T cell activation in the periphery and the CNS as well as the generation of anti-MOG antibodies (Ab).
  
  
  CONCLUSIONS
  AID(-/-) mice exhibit reduced severity and incidence of EAE. This suggests that the secondary diversification of the B cell receptor is required for B cells to exert their full encephalogenic potential during rhMOG-induced EAE, and possibly also during MS.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Georgina
authors.initials: G
authors.lastname: Galicia
authors.forename: Bryant
authors.initials: B
authors.lastname: Boulianne
authors.forename: Natalia
authors.initials: N
authors.lastname: Pikor
authors.forename: Alberto
authors.initials: A
authors.lastname: Martin
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gommerman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase / Q000172:deficiency; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M; D063308:Myelin-Oligodendrocyte Glycoprotein; D011956:Receptors, Cell Surface; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase