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Open Access 01-12-2017 | Research

Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis

Authors: Kathrin Bail, Quirin Notz, Damiano M. Rovituso, Andrea Schampel, Marie Wunsch, Tobias Koeniger, Verena Schropp, Richa Bharti, Claus-Juergen Scholz, Konrad U. Foerstner, Christoph Kleinschnitz, Stefanie Kuerten

Published in: Journal of Neuroinflammation | Issue 1/2017

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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Title: Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis
Authors: Kathrin Bail
Quirin Notz
Damiano M. Rovituso
Andrea Schampel
Marie Wunsch
Tobias Koeniger
Verena Schropp
Richa Bharti
Claus-Juergen Scholz
Konrad U. Foerstner
Christoph Kleinschnitz
Stefanie Kuerten
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-017-0924-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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