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PMID: 11274428 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Montrasio F, Cozzio A, Flechsig E, Rossi D, Klein MA, Rülicke T, Raeber AJ, Vosshenrich CA, Proft J, Aguzzi A, Weissmann C

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.

MeSH Terms
Animals B-Lymphocytes/metabolism Central Nervous System/metabolism Dendritic Cells, Follicular/metabolism Mice Mice, Knockout Mice, Transgenic Prions/genetics,metabolism Spleen/metabolism
Chemicals
Prions
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Montrasio F
Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Cozzio A
Flechsig E
Rossi D
Klein M A
Rülicke T
Raeber A J
Vosshenrich C A
Proft J
Aguzzi A
Weissmann C
References (30)
30 references, click to expand
  1. Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells.
    Nat Med. 1999 Nov;5(11):1308-12 PMID: 10545999
  2. PrP-dependent association of prions with splenic but not circulating lymphocytes of scrapie-infected mice.
    EMBO J. 1999 May 17;18(10):2702-6 PMID: 10329617
  3. Impaired prion replication in spleens of mice lacking functional follicular dendritic cells.
    Science. 2000 May 19;288(5469):1257-9 PMID: 10818004
  4. Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy.
    J Pathol. 2000 Jul;191(3):323-32 PMID: 10878556
  5. Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie.
    Nat Med. 2000 Jul;6(7):719-20 PMID: 10888894
  6. Measurement of the scrapie agent using an incubation time interval assay.
    Ann Neurol. 1982 Apr;11(4):353-8 PMID: 6808890
  7. B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes.
    J Immunol. 1983 Jul;131(1):244-50 PMID: 6408173
  8. A novel approach for preparing anti-T cell receptor constant region antibodies.
    Eur J Immunol. 1986 Jul;16(7):851-4 PMID: 3087759
  9. Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy.
    J Virol Methods. 1989 Apr-May;24(1-2):215-21 PMID: 2569471
  10. Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease.
    J Virol. 1991 Nov;65(11):6292-5 PMID: 1681118
  11. The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt-Jakob disease.
    Am J Pathol. 1992 Jun;140(6):1411-20 PMID: 1376559
  12. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice.
    J Pathol. 1992 Dec;168(4):413-8 PMID: 1362440
  13. Constitutive expression of high levels of soluble mouse CD4 in transgenic mice does not interfere with their immune function.
    Eur J Immunol. 1993 Feb;23(2):511-6 PMID: 8094673
  14. Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface.
    Cell. 1993 Mar 26;72(6):847-56 PMID: 7916655
  15. Mice devoid of PrP are resistant to scrapie.
    Cell. 1993 Jul 2;73(7):1339-47 PMID: 8100741
  16. Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system.
    Mol Cell Biol. 1994 Feb;14(2):1500-9 PMID: 7507207
  17. Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development.
    Mol Cell Biol. 1994 Jun;14(6):3884-94 PMID: 7515149
  18. Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors.
    J Immunol. 1995 Jan 1;154(1):33-46 PMID: 7995952
  19. PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology.
    Neurodegeneration. 1994 Dec;3(4):331-40 PMID: 7842304
  20. Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.
    J Virol. 1995 Dec;69(12):7586-92 PMID: 7494265
  21. Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie.
    EMBO J. 1996 Mar 15;15(6):1255-64 PMID: 8635458
  22. High prion and PrPSc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted PrP gene.
    Mol Med. 1994 Nov;1(1):19-30 PMID: 8790598
  23. Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system.
    Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13148-51 PMID: 8917559
  24. PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain.
    Nature. 1997 Sep 4;389(6646):69-73 PMID: 9288968
  25. Prion (PrPSc)-specific epitope defined by a monoclonal antibody.
    Nature. 1997 Nov 6;390(6655):74-7 PMID: 9363892
  26. A crucial role for B cells in neuroinvasive scrapie.
    Nature. 1997 Dec 18-25;390(6661):687-90 PMID: 9414161
  27. The sequential role of lymphotoxin and B cells in the development of splenic follicles.
    J Exp Med. 1998 Apr 6;187(7):997-1007 PMID: 9529316
  28. PrP expression in B lymphocytes is not required for prion neuroinvasion.
    Nat Med. 1998 Dec;4(12):1429-33 PMID: 9846583
  29. Ectopic expression of prion protein (PrP) in T lymphocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3987-92 PMID: 10097150
  30. Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: role of prion protein expression in peripheral nerves and spleen.
    J Virol. 2000 Jan;74(2):828-33 PMID: 10623745
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2001-03-27
Epub
2001-00-13
Pages
4034-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC31174
Subset
IM
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