B lymphocyte-restricted expression of prion protein does not enable prion replication in prion protein knockout mice

doi:10.1073/pnas.051609398

B lymphocyte-restricted expression of prion protein does not enable prion replication in prion protein knockout mice

^*Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; ^†Department of Pathology, Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; ^¶Biologisches Zentrallabor, Sternwartstrasse 6, CH-8091 Zurich, Switzerland; and ^**Institute for Genetics, Weyertalstrasse 121, D-50931 Cologne, Germany

Contributed by Charles Weissmann

Abstract

Prion replication in spleen and neuroinvasion after i.p. inoculation of mice is impaired in forms of immunodeficiency where mature B lymphocytes are lacking. In spleens of wild-type mice, infectivity is associated with B and T lymphocytes and stroma but not with circulating lymphocytes. We generated transgenic prion protein knockout mice overexpressing prion protein in B lymphocytes and found that they failed to accumulate prions in spleen after i.p. inoculation. We conclude that splenic B lymphocytes are not prion-replication competent and that they acquire prions from other cells, most likely follicular dendritic cells with which they closely associate and whose maturation depends on them.

Footnotes

↵ ‡ Present address: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
↵ § Present address: MRC Prion Unit/Neurogenetics, Imperial College School of Medicine at St. Mary's, Norfolk Place, London W2 1PG, United Kingdom.
↵ ‖ Present address: Cytos Biotechnology AG, Wagistrasse 21, CH-8952 Zurich-Schlieren, Switzerland.
↵ ‡‡ Present address: Departement d'Immunologie, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris, France.
↵ †† To whom reprint requests should be addressed. E-mail: c.weissmann{at}ic.ac.uk.
Abbreviations:

CNS,

central nervous system;

FACS,

fluorescence-activated cell sorting;

FDC,

follicular dendritic cell;

PE,

phycoerythrin;

PrP,

prion protein