title: PrP expression in B lymphocytes is not required for prion neuroinvasion.
abstract: 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.
authors.affiliation: Institute of Neuropathology, University of Zürich, Switzerland.
authors.forename: M A
authors.initials: MA
authors.lastname: Klein
authors.forename: R
authors.initials: R
authors.lastname: Frigg
authors.forename: A J
authors.initials: AJ
authors.lastname: Raeber
authors.forename: E
authors.initials: E
authors.lastname: Flechsig
authors.forename: I
authors.initials: I
authors.lastname: Hegyi
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: C
authors.initials: C
authors.lastname: Weissmann
authors.forename: A
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015415:Biomarkers; D002417:Cattle; D002490:Central Nervous System / Q000276:immunology / Q000821:virology*; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008970:Molecular Weight; D017933:Peripheral Nervous System / Q000276:immunology / Q000821:virology*; D018620:PrPSc Proteins / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology; D011328:Prions / Q000096:biosynthesis / Q000276:immunology*; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D018620:PrPSc Proteins; D011328:Prions; C064658:RAG-1 protein