Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis
Bail K, Notz Q, Rovituso DM, Schampel A, Wunsch M, Koeniger T, Schropp V, Bharti R, Scholz CJ, Foerstner KU, Kleinschnitz C, Kuerten S (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 14
Journal Issue: 1
DOI: 10.1186/s12974-017-0924-4
Abstract
BACKGROUND: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). METHODS: MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P1 receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. RESULTS: FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220+ B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. CONCLUSIONS: The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.
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APA:
Bail, K., Notz, Q., Rovituso, D.M., Schampel, A., Wunsch, M., Koeniger, T.,... Kuerten, S. (2017). Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis. Journal of Neuroinflammation, 14(1). https://doi.org/10.1186/s12974-017-0924-4
MLA:
Bail, Kathrin, et al. "Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis." Journal of Neuroinflammation 14.1 (2017).
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