{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:15:18Z","timestamp":1791137718566,"version":"4.1.0"},"reference-count":53,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abnormal isoforms of the prion protein (PrPSc) that cause prion diseases are propagated and spread within the body by \u201ccarrier\u201d cell(s). Cells of the immune system have been strongly implicated in this process. In particular, PrPSc is known to accumulate on follicular dendritic cells (FDCs) in individuals affected by variant Creutzfeld-Jakob disease. However, FDCs do not migrate widely and the natural history of prion disorders suggests other cells may be required for the transport of PrPSc from the site of ingestion to lymphoid organs and the central nervous system. Substantial evidence suggests that the spread of PrPSc requires bone marrow-derived cells that express normal cellular prion protein (PrPC). This study examined the expression of PrPC on bone marrow\u2013derived cells that interact with lymphoid follicles. High levels of PrPC are present on myeloid dendritic cells (DCs) that surround the splenic white pulp. These myeloid DCs are ontologically and functionally distinct from the FDCs. Consistent with these observations, expression of PrPC was strongly induced during the generation of mature myeloid DCs in vitro. In these cells PrPCcolocalized with major histocompatibility complex class II molecules at the level of light microscopy. Furthermore, given the close anatomic and functional connection of myeloid DCs with lymphoid follicles, these results raise the possibility that myeloid DCs may play a role in the propagation of PrPSc in humans.<\/jats:p>","DOI":"10.1182\/blood.v98.13.3733","type":"journal-article","created":{"date-parts":[[2002,10,28]],"date-time":"2002-10-28T20:44:12Z","timestamp":1035837852000},"page":"3733-3738","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":58,"title":["The normal cellular prion protein is strongly expressed by myeloid dendritic cells"],"prefix":"10.1182","volume":"98","author":[{"given":"John","family":"Burthem","sequence":"first","affiliation":[{"name":"From the Nuffield Department of Biochemistry and Cellular Science, University of Oxford, and National Blood Service, John Radcliffe Hospital, Oxford, United Kingdom; and Department of Biomedical Sciences, UMIST, Manchester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Urban","sequence":"additional","affiliation":[{"name":"From the Nuffield Department of Biochemistry and Cellular Science, University of Oxford, and National Blood Service, John Radcliffe Hospital, Oxford, United Kingdom; and Department of Biomedical Sciences, UMIST, Manchester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Pain","sequence":"additional","affiliation":[{"name":"From the Nuffield Department of Biochemistry and Cellular Science, University of Oxford, and National Blood Service, John Radcliffe Hospital, Oxford, United Kingdom; and Department of Biomedical Sciences, UMIST, Manchester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"From the Nuffield Department of Biochemistry and Cellular Science, University of Oxford, and National Blood Service, John Radcliffe Hospital, Oxford, United Kingdom; and Department of Biomedical Sciences, UMIST, Manchester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021216592660600_B1","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/3955","article-title":"B lymphocytes in prion neuroinvasion: central or peripheral players?","volume":"4","author":"Collinge","year":"1998","journal-title":"Nat Med."},{"key":"2020021216592660600_B2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0092-8674(00)81163-0","article-title":"Prion protein biology.","volume":"93","author":"Pruisner","year":"1998","journal-title":"Cell."},{"key":"2020021216592660600_B3","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1046\/j.1365-2141.1999.01457.x","article-title":"The impact of new-variant Creutzfeld-Jacob disease on blood transfusion practice.","volume":"106","author":"Turner","year":"1999","journal-title":"Br J Haematol."},{"key":"2020021216592660600_B4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0887-7963(99)80001-7","article-title":"New variant Creutzfeldt-Jakob disease (nvCJD): the risk of transmission by blood transfusion and the potential benefit of leukocyte-reduction of blood components.","volume":"13","author":"Murphy","year":"1999","journal-title":"Transfus Med Rev."},{"key":"2020021216592660600_B5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/1531-8249(200005)47:5<575::AID-ANA4>3.0.CO;2-W","article-title":"Diagnosis of new variant Creutzfeldt-Jakob disease.","volume":"47","author":"Will","year":"2000","journal-title":"Ann Neurol."},{"key":"2020021216592660600_B6","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.1128\/JVI.65.11.6292-6295.1991","article-title":"Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease.","volume":"65","author":"Kitamoto","year":"1991","journal-title":"J Virol."},{"key":"2020021216592660600_B7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/path.1711680412","article-title":"PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice.","volume":"168","author":"McBride","year":"1992","journal-title":"J Pathol."},{"key":"2020021216592660600_B8","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(98)12075-5","article-title":"Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples.","volume":"353","author":"Hill","year":"1999","journal-title":"Lancet."},{"key":"2020021216592660600_B9","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/15264","article-title":"Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells.","volume":"5","author":"Brown","year":"1999","journal-title":"Nat Med."},{"key":"2020021216592660600_B10","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1126\/science.288.5469.1257","article-title":"Impaired prion replication in spleens of mice lacking functional follicular dendritic cells.","volume":"288","author":"Montrasio","year":"2000","journal-title":"Science."},{"key":"2020021216592660600_B11","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/37789","article-title":"A crucial role for B cells in neuroinvasive scrapie.","volume":"390","author":"Klein","year":"1997","journal-title":"Nature."},{"key":"2020021216592660600_B12","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1038\/4022","article-title":"PrP expression in B lymphocytes is not required for prion neuroinvasion.","volume":"4","author":"Klein","year":"1998","journal-title":"Nat Med."},{"key":"2020021216592660600_B13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1600-065X.1990.tb00573.x","article-title":"Follicular cells as accessory cells.","volume":"117","author":"Tew","year":"1990","journal-title":"Immunol Rev."},{"key":"2020021216592660600_B14","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s004010051109","article-title":"Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies.","volume":"98","author":"Hainfellner","year":"1999","journal-title":"Acta Neuropathol."},{"key":"2020021216592660600_B15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0168-1702(89)90039-7","article-title":"The role of the spleen in the neuroinvasion of scrapie in mice.","volume":"12","author":"Kimberlin","year":"1989","journal-title":"Virus Res."},{"key":"2020021216592660600_B16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/37981","article-title":"PrPexpressing tissue required for transfer of scrapie infectivity from spleen to brain.","volume":"389","author":"Blattler","year":"1997","journal-title":"Nature."},{"key":"2020021216592660600_B17","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1099\/0022-1317-76-10-2583","article-title":"A cellular form of prion protein (PrPC) exists in many non-neuronal tissues of sheep.","volume":"76","author":"Horiuchi","year":"1995","journal-title":"J Gen Virol."},{"key":"2020021216592660600_B18","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/j.1469-445X.2000.02091.x","article-title":"Neuroinvasion of prions: insights from mouse models.","volume":"85","author":"Bradner","year":"2000","journal-title":"Exp Physiol."},{"key":"2020021216592660600_B19","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1182\/blood.V91.5.1556","article-title":"Prion protein expression in human leukocyte differentiation.","volume":"91","author":"Dodelet","year":"1998","journal-title":"Blood."},{"key":"2020021216592660600_B20","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1046\/j.1365-2141.1999.01789.x","article-title":"Distribution of cell-associated prion protein in normal adult blood determined by flow cytometry.","volume":"107","author":"Barclay","year":"1999","journal-title":"Br J Haematol."},{"key":"2020021216592660600_B21","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1046\/j.1365-2141.2000.01881.x","article-title":"Differential constitutive and activation-dependent expression of prion protein in human peripheral blood leucocytes.","volume":"108","author":"Durig","year":"2000","journal-title":"Br J Haematol."},{"key":"2020021216592660600_B22","first-page":"475","article-title":"Differential expression of cellular prion protein on human blood and tonsil lymphocytes.","volume":"85","author":"Antoine","year":"2000","journal-title":"Haematologica."},{"key":"2020021216592660600_B23","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1084\/jem.182.2.389","article-title":"Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: down-regulation by cytokines and bacterial products.","volume":"182","author":"Sallusto","year":"1995","journal-title":"J Exp Med."},{"key":"2020021216592660600_B24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/21900","article-title":"Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells.","volume":"400","author":"Urban","year":"1999","journal-title":"Nature."},{"key":"2020021216592660600_B25","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.4049\/jimmunol.160.5.2166","article-title":"Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover.","volume":"160","author":"Leenan","year":"1998","journal-title":"J Immunol."},{"key":"2020021216592660600_B26","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0002-9440(10)65744-6","article-title":"Endogenous proteolytic cleavage of normal and disease-associated isoforms of the human prion protein in neural and non-neural tissues.","volume":"153","author":"Jimenez-Huete","year":"1998","journal-title":"Am J Pathol."},{"key":"2020021216592660600_B27","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S0167-5699(00)01696-0","article-title":"Follicular dendritic cells in TSE pathogenesis.","volume":"21","author":"Bruce","year":"2000","journal-title":"Immunol Today."},{"key":"2020021216592660600_B28","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.1128\/JVI.65.11.6292-6295.1991","article-title":"Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfelt-Jakob disease.","volume":"65","author":"Kitamoto-T Muramoto","year":"1991","journal-title":"J Virol."},{"key":"2020021216592660600_B29","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1099\/0022-1317-81-12-3115","article-title":"Early accumulation of PrPSc in gut associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie.","volume":"81","author":"Andreoletti-O","year":"2000","journal-title":"J Gen Virol."},{"key":"2020021216592660600_B30","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1097\/00001756-199805110-00032","article-title":"Microglial expression of the prion protein.","volume":"9","author":"Brown","year":"1998","journal-title":"Neuroreport."},{"key":"2020021216592660600_B31","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev.iy.07.040189.000515","article-title":"Microanatomy of lymphoid tissue during humoral immune responses: structure function relationships.","volume":"7","author":"Szakal","year":"1989","journal-title":"Ann Rev Immunol."},{"key":"2020021216592660600_B32","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.4049\/jimmunol.160.3.1078","article-title":"Follicular dendritic cell (FDC) precursors in primary lymphoid tissues.","volume":"160","author":"Kapasi","year":"1998","journal-title":"J Immunol."},{"key":"2020021216592660600_B33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s004410051036","article-title":"Distribution and submicroscopic immunogold localization of cellular prion protein (PrPC) in extracerebral tissues.","volume":"292","author":"Fournier","year":"1998","journal-title":"Cell Tissue Res."},{"key":"2020021216592660600_B34","doi-asserted-by":"crossref","first-page":"8879","DOI":"10.1021\/bi00490a001","article-title":"Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein.","volume":"29","author":"Stahl","year":"1990","journal-title":"Biochemistry."},{"key":"2020021216592660600_B35","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S0167-5699(99)01494-2","article-title":"Microdomains in lymphocyte signalling: beyond GPIanchored proteins.","volume":"21","author":"Ilangumaran","year":"2000","journal-title":"Immunol Today."},{"key":"2020021216592660600_B36","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0014-5793(98)00372-X","article-title":"Prion protein structural features indicate possible relations to signal peptidases.","volume":"426","author":"Glockshuber","year":"1998","journal-title":"FEBS Lett."},{"key":"2020021216592660600_B37","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0092-8674(90)90225-4","article-title":"Cellular isoform of the scrapie agent protein participates in lymphocyte activation.","volume":"61","author":"Cashman","year":"1990","journal-title":"Cell."},{"key":"2020021216592660600_B38","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1042\/bj3200563","article-title":"Activation effects of a prion protein fragment (PrP-[106-126]) on human leucocytes.","volume":"320","author":"Diomede","year":"1996","journal-title":"Biochem J."},{"key":"2020021216592660600_B39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1046\/j.1365-2567.1997.00331.x","article-title":"T-lymphocyte activation and the cellular form of the prion protein.","volume":"92","author":"Mabbott","year":"1997","journal-title":"Immunology."},{"key":"2020021216592660600_B40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0008-8749(88)90061-5","article-title":"Accessory cell requirements for the mixed-leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells.","volume":"111","author":"Young","year":"1988","journal-title":"Cell Immunol."},{"key":"2020021216592660600_B41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0002-9440(10)64517-8","article-title":"Gene expression profile in prion protein-deficient fibroblasts in culture.","volume":"157","author":"Satoh","year":"2000","journal-title":"Am J Pathol."},{"key":"2020021216592660600_B42","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0169-328X(99)00334-4","article-title":"Cellular prion protein binds laminin and mediates neuritogenesis.","volume":"76","author":"AU Graner","year":"2000","journal-title":"Mol Brain Res."},{"key":"2020021216592660600_B43","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1126\/science.289.5486.1925","article-title":"Signal transduction through prion protein.","volume":"289","author":"Mouillet-Richard","year":"2000","journal-title":"Science."},{"key":"2020021216592660600_B44","doi-asserted-by":"crossref","first-page":"33107","DOI":"10.1074\/jbc.273.50.33107","article-title":"Copper stimulates endocytosis of the prion protein.","volume":"273","author":"Pauly","year":"1998","journal-title":"J Biol Chem."},{"key":"2020021216592660600_B45","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1083\/jcb.125.6.1239","article-title":"A glycolipid-anchored prion protein is endocytosed via clatharin-coated pits.","volume":"125","author":"Shyng-SL","year":"1994","journal-title":"J Cell Biol."},{"key":"2020021216592660600_B46","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1073\/pnas.96.7.3987","article-title":"Ectopic expression of prion protein (PrP) in T lymphocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication.","volume":"96","author":"Raeber","year":"1999","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021216592660600_B47","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1750-3639.1995.tb00579.x","article-title":"Prion protein transgenes and the neuropathology in prion diseases.","volume":"5","author":"DeArmond-S Prusiner","year":"1995","journal-title":"Brain Pathol."},{"key":"2020021216592660600_B48","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1099\/0022-1317-81-11-2813","article-title":"PrPC expression in the peripheral nervous system is a determinant of prion neuroinvasion.","volume":"81","author":"Glatzel-M","year":"2000","journal-title":"J Gen Virol."},{"key":"2020021216592660600_B49","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity.","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature."},{"key":"2020021216592660600_B50","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1146\/annurev.immunol.18.1.767","article-title":"Immunobiology of dendritic cells.","volume":"18","author":"Banchereau","year":"2000","journal-title":"Ann Rev Immunol."},{"key":"2020021216592660600_B51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/(SICI)1096-9861(19990322)405:4<553::AID-CNE8>3.0.CO;2-6","article-title":"Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations.","volume":"405","author":"McMenamin","year":"1999","journal-title":"J Comp Neurol."},{"key":"2020021216592660600_B52","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0165-5728(99)00240-4","article-title":"Monocyte-derived IL-10-secreting dendritic cells in choroid plexus epithelium.","volume":"105","author":"Serot","year":"2000","journal-title":"J Neuroimmunol."},{"key":"2020021216592660600_B53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/384364a0","article-title":"Dendritic cells capable of stimulating T cells in germinal centres.","volume":"384","author":"Grouard","year":"1996","journal-title":"Nature."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/98\/13\/3733\/1679337\/h8240103733.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/98\/13\/3733\/1679337\/h8240103733.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T20:10:39Z","timestamp":1682280639000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/98\/13\/3733\/90246\/The-normal-cellular-prion-protein-is-strongly"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,15]]},"references-count":53,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2001,12,15]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v98.13.3733","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2001,12,15]]}}}