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Title

MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies
Authors
Molnarfi, Nicolas
Schulze-Topphoff, Ulf
Weber, Martin S
Patarroyo, Juan C
Prod'homme, Thomas
Varrin-Doyer, Michel
Shetty, Aparna
Linington, Christopher
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Published in The Journal of experimental medicine. 2013, vol. 210, no. 13, p. 2921-2937
Abstract 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.
Keywords Animals — Antigen-Presenting Cells / immunology — B-Lymphocytes / immunology — Cell Proliferation — Cell Separation — Central Nervous System / immunology — Cytokines / metabolism — Encephalomyelitis, Autoimmune, Experimental / genetics — Encephalomyelitis, Autoimmune, Experimental / immunology — Flow Cytometry — Gene Expression Regulation — Genes, MHC Class II — Genetic Predisposition to Disease — Immunoglobulins / immunology — Interleukin-6 / metabolism — Mice — Mice, Inbred C57BL — Mice, Transgenic — Myelin Sheath / immunology — Th1 Cells / immunology — Th17 Cells / immunology
Identifiers
PMID: 24323356
PMCID: PMC3865476
Full text
Article (Published version) (4.4 MB) - public document Free access
Other version: https://rupress.org/jem/article/210/13/2921/41482/MHC-class-II-dependent-B-cell-APC-function-is
Project
Swiss National Science Foundation: PA00P3-119532
Citation
(ISO format) 		MOLNARFI, Nicolas et al. MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. In: The Journal of experimental medicine, 2013, vol. 210, n° 13, p. 2921-2937. doi: 10.1084/jem.20130699 https://archive-ouverte.unige.ch/unige:156739

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Deposited on : 2021-11-26

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