@phdthesis{Notz2019,
  author    = {Notz, Quirin Julius},
  title     = {Der Einfluss von Fingolimod auf die autoreaktive B-Zell-Antwort in einem B-Zell-abh{\"a}ngigen Mausmodell der Multiplen Sklerose},
  doi       = {10.25972/OPUS-19154},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191540},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Die MP4-induzierte experimentelle autoimmune Encephalomyelitis (EAE) erlaubt eine fokussierte Betrachtung von B-Zellen, die eine wichtige Rolle bei der Pathogenese der Multiplen Sklerose (MS) spielen. Es konnte zum Beispiel gezeigt werden, dass das Vorhandensein von B-Zell-Aggregaten im zentralen Nervensystem (ZNS) von MS-Patienten mit einem aggravierten Krankheitsverlauf assoziiert war. Diese Follikel k{\"o}nnten dabei als ektope lymphatische Strukturen den Immunprozess aktiv gestalten und somit ein therapeutisches Ziel darstellen. In der vorliegenden Studie wurde der Effekt des Sphingosin-1-Phosphat-Rezeptor-Modulators Fingolimod (FTY720) auf die autoreaktive B-Zell-Antwort und speziell die Bildung von B-Zell-Aggregaten im Kleinhirn der MP4-EAE-M{\"a}use untersucht.},
  subject      = {Multiple Sklerose},
  language  = {de}
}
@article{BailNotzRovitusoetal.2017,
  author    = {Bail, Kathrin and Notz, Quirin and Rovituso, Damiano M. and Schampel, Andrea and Wunsch, Marie and Koeniger, Tobias and Schropp, Verena and Bharti, Richa and Scholz, Claus-Juergen and Foerstner, Konrad U. and Kleinschnitz, Christoph and Kuerten, Stefanie},
  title     = {Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.},
  series = {Journal of Neuroinflammation},
  volume    = {14},
  journal   = {Journal of Neuroinflammation},
  number    = {148},
  doi       = {10.1186/s12974-017-0924-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157869},
  year      = {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. S1P\(_{1}\) 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.},
  language  = {en}
}