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

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 AnimalsAntigen-Presenting Cells / immunologyB-Lymphocytes / immunologyCell ProliferationCell SeparationCentral Nervous System / immunologyCytokines / metabolismEncephalomyelitis, Autoimmune, Experimental / geneticsEncephalomyelitis, Autoimmune, Experimental / immunologyFlow CytometryGene Expression RegulationGenes, MHC Class IIGenetic Predisposition to DiseaseImmunoglobulins / immunologyInterleukin-6 / metabolismMiceMice, Inbred C57BLMice, TransgenicMyelin Sheath / immunologyTh1 Cells / immunologyTh17 Cells / immunology
PMID: 24323356
PMCID: PMC3865476
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Swiss National Science Foundation: PA00P3-119532
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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

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Deposited on : 2021-11-26

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