NR AGOI
AU Klein,M.A.; Frigg,R.; Raeber,A.J.; Flechsig,E.; Hegyi,I.; Zinkernagel,R.M.; Weissmann,C.; Aguzzi,A.
TI PrP expression in B lymphocytes is not required for prion neuroinvasion
QU Nature Medicine 1998 Dec; 4(12): 1429-33
KI Nat Med. 1998 Dec;4(12):1369-70. PMID: 9846572
PT journal article
AB Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy, new variant Creutzfeldt-Jakob disease, 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. We have now assessed whether expression of the cellular prion protein, PrPc, 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.
IN Der Aufbau eines neuen Immunsystems bei immundefizienten SCID- oder Rag-1(-/-)-Mäusen durch fötale Leberzellen, macht die Empfänger anfällig für periphere Scrapie-Infektionen, auch wenn wenn die Spendermäuse kein Prionprotein exprimieren oder keine T-Lymphozyten produzieren. Nur reife B-Lymphozyten mit oder ohne Prionproteine müssen vorhanden sein, damit Mäuse empfänglich für periphere Scrapie-Infektionen werden. Möglicherweise sind die B-Lymphozyten aber nur indirekt erforderlich, weil beispielsweise follikuläre dendritische Zellen nicht ohne B-Lymphozyten reifen können.
ZR 22
MH Animal; B-Lymphocytes/*immunology/*virology; Biological Markers; Cattle; Central Nervous System/immunology/*virology; Encephalopathy, Bovine Spongiform/metabolism/pathology; Homeodomain Proteins/analysis; Mice; Mice, Inbred C57BL; Mice, SCID; Molecular Weight; Peripheral Nervous System/immunology/*virology; PrPsc Proteins/immunology; Prion Diseases/immunology; Prions/biosynthesis/*immunology; Support, Non-U.S. Gov't; Virus Replication
AD Institute of Neuropathology, University of Zürich, Switzerland.
SP englisch
PO USA