PrP expression in B lymphocytes is not required for prion neuroinvasion (original) (raw)

Nature Medicine volume 4, pages 1429–1433 (1998)Cite this article

Abstract

Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy, new variant Creutzfeldt-Jakob disease 1 , kuru and most cases of iatrogenic Creutzfeldt-Jakob disease. In mouse scrapie, prion infectivity accumulates in lymphoid organs, and the absence of mature B lymphocytes prevents peripherally administered prions from inducing central nervous system disease 2 . We have now assessed whether expression of the cellular prion protein, PrP C , is required for B lymphocytes to mediate neuroinvasion. We found that repopulation of SCID and Rag -1 -/- mice with fetal liver cells from either PrP-expressing or PrP-deficient mice and from T-cell deficient mice, but not from B-cell deficient mice, is equally efficient in restoring neuroinvasion after intraperitoneal inoculation of scrapie prions. These results indicate that cells whose maturation depends on B cells or their products, such as follicular dendritic cells, may enhance neuroinvasion. Alternatively, B cells may transport prions to the nervous system by a PrP-independent mechanism.

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Acknowledgements

We thank A. Burlet, M. König, and N. Wey for technical help; T. Bächi for help with confocal microscopy; K. Rajewsky for μMT mice; and M. Kosco-Vilbois for the FDC-M1 antibody. M.A.K. is supported by a fellowship of the Deutsche Forschungsgemeinschaft. This work is supported by the Kanton of Zürich, the Bundesämter für Gesundheit, Veterinärwesen, Bildung und Wissenschaft, and by grants of the Swiss National Research Program NFP38/NFP38+ to A.A., A.J.R., R.M.Z., and C.W.

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Author notes

  1. Rolf M. Zinkernagel: Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland M.A.K & R.F. contributed equally to this study.

Authors and Affiliations

  1. Institute of Neuropathology, University of Zürich, Zürich, Switzerland
    Michael A. Klein, Rico Frigg, Alex J. Raeber, Ivan Hegyi & Adriano Aguzzi
  2. Institute of Molecular Biology, University of Zürich, Zürich, Switzerland
    Eckhard Flechsig & Charles Weissmann

Authors

  1. Michael A. Klein
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  2. Rico Frigg
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  3. Alex J. Raeber
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  4. Eckhard Flechsig
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  5. Ivan Hegyi
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  6. Rolf M. Zinkernagel
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  7. Charles Weissmann
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  8. Adriano Aguzzi
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Corresponding author

Correspondence toAdriano Aguzzi.

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Klein, M., Frigg, R., Raeber, A. et al. PrP expression in B lymphocytes is not required for prion neuroinvasion .Nat Med 4, 1429–1433 (1998). https://doi.org/10.1038/4022

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