Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease

Author:

Flach Anne-Christine,Litke Tanja,Strauss Judith,Haberl Michael,Gómez César Cordero,Reindl Markus,Saiz Albert,Fehling Hans-Jörg,Wienands Jürgen,Odoardi Francesca,Lühder Fred,Flügel Alexander

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.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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