title: Inhibitory role of CD19 in the progression of experimental autoimmune encephalomyelitis by regulating cytokine response.
abstract: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nerve system that is considered a T helper type 1 (Th1)-mediated autoimmune disease. EAE currently serves as an experimental animal model for multiple sclerosis in human. Cytokines, such as interferon-gamma and interleukin-10, play a key role in the development and remission of EAE. Recent studies have also shown a role for B cells in the pathogenesis of EAE. Therefore, we examined the role of CD19, a B cell-specific surface molecule that defines signaling thresholds critical for B-cell responses and autoimmunity, on the development of EAE. Following immunization with myelin oligodendrocyte glycoprotein (MOG) peptide, CD19-deficient (CD19(-/-)) mice exhibited higher clinical and pathological severity scores of EAE than wild-type mice. The increased severity of EAE in CD19(-/-) mice was associated with polarized Th1 cytokines in the inflamed central nerve system but not with anti-MOG antibodies in the serum. MOG-primed CD19(-/-) B cells produced high levels of interferon-gamma, and transfer of MOG-primed CD19(-/-) B cells to wild-type mice worsened the disease. Thus, CD19 modulates the Th1/Th2 cytokine balance in B cells and plays a critical role as a suppressive molecule in the development of EAE.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Komura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D018941:Antigens, CD19 / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007136:Immunoglobulins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D016207:Cytokines; D007136:Immunoglobulins; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016753:Interleukin-10; D007371:Interferon-gamma