Abstract
Although prion proteins are most efficiently propagated through intracerebral inoculation, peripheral administration has caused the diseases kuru, iatrogenic Creutzfeldt–Jakob disease (CJD), bovine spongiform encephalopathy (BSE) and new-variant CJD1,2. The development of neurological disease after peripheral inoculation depends on prion expansion within cells of the lymphoreticular system3,4. Here we investigate the identity of these cells by using a panel of immune-deficient mice inoculated with prions intraperitoneally: we found that defects affecting only T lymphocytes had no apparent effect, but that all mutations that disrupted the differentiation and response of B lymphocytes prevented the development of clinical scrapie. As an absence of B cells and of antibodies correlates with severe defects in follicular dendritic cells, a lack of any of these three components may prevent the development of clinical scrapie. However, we found that scrapie developed after peripheral inoculation in mice expressing immunoglobulins that were exclusively of the M subclass and without detectable specificity for the normal form of the prion PrPc, and in mice which had differentiated B cells but no functional follicular dendritic cells. We conclude that differentiated B cells are crucial for neuroinvasion by scrapie, regardless of the specificity of their receptors.
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Acknowledgements
We thank C. Weissmann for discussion, and M. König, A. Burlet and N. Wey for technical help. M.K. is supported by a fellowship from 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 to A.A., A.R. and R.Z.
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Klein, M., Frigg, R., Flechsig, E. et al. A crucial role for B cells in neuroinvasive scrapie. Nature 390, 687–690 (1997). https://doi.org/10.1038/37789
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DOI: https://doi.org/10.1038/37789
