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MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies

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Wekerle,  Hartmut
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Zitation

Molnarfi, N., Schulze-Topphoff, U., Weber, M. S., Patarroyo, J. C., Prod'homme, T., Varrin-Doyer, M., et al. (2013). MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. JOURNAL OF EXPERIMENTAL MEDICINE, 210(13), 2921-2937. doi:10.1084/jem.20130699.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0015-18C7-C
Zusammenfassung
Whether B cells serve as antigen-presenting cells (APCs) for activation of pathogenic T cells in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) is unclear. To evaluate their role as APCs, we engineered mice selectively deficient in MHC II on B cells (B-MHC II-/-), and to distinguish this function from antibody production, we created transgenic (Tg) mice that express the myelin oligodendrocyte glycoprotein (MOG)-specific B cell receptor (BCR; IgH(MOG-mem)) but cannot secrete antibodies. B-MHC II-/- mice were resistant to EAE induced by recombinant human MOG (rhMOG), a T cell-and B cell-dependent autoantigen, and exhibited diminished Th1 and Th17 responses, suggesting a role for B cell APC function. In comparison, selective B cell IL-6 deficiency reduced EAE susceptibility and Th17 responses alone. Administration of MOG-specific antibodies only partially restored EAE susceptibility in B-MHC II-/- mice. In the absence of antibodies, IgH(MOG-mem) mice, but not mice expressing a BCR of irrelevant specificity, were fully susceptible to acute rhMOG-induced EAE, also demonstrating the importance of BCR specificity. Spontaneous opticospinal EAE and meningeal follicle-like structures were observed in IgH(MOG-mem) mice crossed with MOG-specific TCR Tg mice. Thus, B cells provide a critical cellular function in pathogenesis of central nervous system autoimmunity independent of their humoral involvement, findings which may be relevant to B cell-targeted therapies.