Impaired prion replication in spleens of mice lacking functional follicular dendritic cells.
In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes and in the stroma, which contains follicular dendritic cells (FDCs). Formation and maintenance of mature FDCs require the presence of B cells expressing membrane-bound lymphotoxin-alpha/beta. Treatment of mice with soluble lymphotoxin-beta receptor results in the disappearance of mature FDCs from the spleen. We show that this treatment abolishes splenic prion accumulation and retards neuroinvasion after intraperitoneal scrapie inoculation. These data provide evidence that FDCs are the principal sites for prion replication in the spleen.
Montrasio
F
F
Institute of Neuropathology, Department of Pathology, University of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Frigg
R
R
Glatzel
M
M
Klein
M A
MA
Mackay
F
F
Aguzzi
A
A
Weissmann
C
C
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D007136:Immunoglobulins / Q000235:genetics; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018620:PrPSc Proteins / Q000008:administration & dosage / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012608:Scrapie / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
D007136:Immunoglobulins; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D018620:PrPSc Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins