Friday, 11 March 2016

Antibodies play their part

Flach AC, Litke T, Strauss J, Haberl M, Gómez CC, Reindl M, Saiz A, Fehling HJ, Wienands J, Odoardi F, Lühder F, Flügel A. Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease. Proc Natl Acad Sci U S A. 2016 Mar 8. pii: 201519608. [Epub ahead of print]

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.
As anti-CD20 antibodies near the clinic, EAEers are beginnng to make EAE into a B cell disease:-).  It isn't......it is a T cell  mediated disease...however B cells and antibodies can clearly impact on  EAE. So here antibodies are being produced and get into the CNS and get taken up by antigen presenting T cell and enhance T cell activity and can now inititate attacks with T cells. We shall see...but in a number of cases there is a very poor antibody response in animals that has been developed disease by the time T cell autoimmunity has developed.

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