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Dual role of B cells with accelerated onset but reduced disease activity in P0106–125-induced experimental autoimmune neuritis of IgH0/0 mice

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Abstract

The role of B cells in autoimmune-mediated diseases of the peripheral nervous system was studied in experimental autoimmune neuritis (EAN) in B cell deficient IgH0/0 C57BL/6J mice having been immunized with P0106–125 peptide. Compared to coisogenic IgH+/+ mice, onset of EAN was accelerated [100% disease incidence at day 9 post immunization (p.i.) vs. day 15 p.i.]. At day 9 p.i., numbers of P0106–125-specific interferon (IFN)-γ-producing CD4+ T cells were increased, while IL-10 mRNA and production were decreased in IgH0/0 mice. Beyond day 9 p.i., declining disease activity and a significant reduction of maximal disease activity were correlated with significantly reduced numbers of IFN-γ-producing CD4+ T cells in IgH0/0 mice as compared with IgH+/+ mice. Correspondingly, neuropathology demonstrated only mild axonal damage, while demyelination and dying back axonopathy with spinal cord motor neuron apoptosis were absent. Thus, depending on the stage of EAN, B cells play a dual, i.e. suppressive and enhancing, role during induction and at height of EAN, respectively. The combined interaction of B cells as well as CD4+ and CD8+ T cells is required for the development of EAN.

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Acknowledgments

The authors thank Mariana Carstov, Elena Fischer, and Anja Tümmermann for expert technical assistance and Hartmut Stützer MD, MSc, Institute of Medical Statistics, Informatics, and Epidemiology, University Hospital of Cologne, Cologne, Germany, for helpful advice with statistical analysis. This study was supported by Else Kröner-Fresenius-Stiftung (P86/08 // A59/08).

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Authors and Affiliations

  1. Department of Neuropathology, University Hospital of Cologne, Kerpener Str. 62, 50924, Cologne, Germany

    Anna Brunn, Monica Sánchez-Ruiz, Manuel Montesinos-Rongen, Tobias Blau & Martina Deckert

  2. Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Cologne, Germany

    Olaf Utermöhlen

  3. Center for Molecular Medicine, Cologne, Germany

    Olaf Utermöhlen

  4. Institute for Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    Dirk Schlüter

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  1. Anna Brunn
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Correspondence to Anna Brunn.

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Supplementary Figure

Dot plots of IL-10-expressing CD4+ T cells and F4/80+ macrophages in PLN and spleen of a P0106-125-immunized IgH0/0 mouse having received rat IgG, an immunized IgH+/+ mouse having received rat IgG and a non-immunized IgH+/+ mouse at d 9 (a), 15 (b), and 22 p.i. (c) including FSC SSC cytograms showing gating strategies (PPT 1,901 kb)

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Brunn, A., Utermöhlen, O., Sánchez-Ruiz, M. et al. Dual role of B cells with accelerated onset but reduced disease activity in P0106–125-induced experimental autoimmune neuritis of IgH0/0 mice. Acta Neuropathol 120, 667–681 (2010). https://doi.org/10.1007/s00401-010-0724-8

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  • DOI: https://doi.org/10.1007/s00401-010-0724-8

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