期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 210, 期 13, 页码 2921-2937出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20130699
关键词
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资金
- Swiss National Science Foundation (SNF) [PA00A-119532]
- European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Foundation
- NMSS [RG 4450A1/T, RG 3913, RG 4768]
- Teva Neuroscience
- National Institutes of Health (NIH) [R01 AI-073737, R01 NS-063008]
- Guthy Jackson Charitable Foundation
- Dana Foundation
- Maisin Foundation
- NIH [R01 AI-043603]
- Deutsche Forschungsgemeinschaft (DFG) [SCHU 2587/1-1]
- [SAF2011-23272]
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.
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