title: Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease.
abstract: Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue.
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Flach
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Tanja
authors.initials: T
authors.lastname: Litke
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Judith
authors.initials: J
authors.lastname: Strauss
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Haberl
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: César Cordero
authors.initials: CC
authors.lastname: Gómez
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, A-6020 Innsbruck, Austria;
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Service of Neurology, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer Casanova, E-08028 Barcelona, Spain;
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Institute for Immunology, University of Ulm, D-89081 Ulm, Germany;
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Fehling
authors.affiliation: Institute for Cellular and Molecular Immunology, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wienands
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany;
authors.forename: Fred
authors.initials: F
authors.lastname: Lühder
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, D-37073 Göttingen, Germany; Max-Planck-Institute for Experimental Medicine Göttingen, D-37075 Göttingen, Germany fluegel@med.uni-goettingen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002454:Cell Differentiation; D002493:Central Nervous System Diseases / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies
keywords: B cells; EAE; autoantibodies; autoimmunity; multiple sclerosis