title: Germinal center B cells are dispensable in prion transport and neuroinvasion.
abstract: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases of animals and humans. Many TSEs are initiated by prion replication in the lymphoreticular system (LRS). The cellular and molecular prerequisites for prion trafficking within the LRS are not fully understood. Here we have manipulated CD40 and its ligand to investigate whether genetic or pharmacological ablation of germinal center B cells (GCBs), which migrate into and out of germinal centers, influences prion pathogenesis. In contrast to previous reports, no alteration of prion pathogenesis was detected in mice lacking CD40L and in mice treated with anti-CD40L antibodies. These results suggest that GCBs alone do not impact peripheral splenic prion transport, replication efficiency, or neuroinvasion, and point to other mechanisms affecting prion transport from lymphoreticular sites of replication to the nervous system.
authors.affiliation: Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Christian
authors.initials: C
authors.lastname: Federau
authors.forename: Lotta von
authors.initials: Lv
authors.lastname: Boehmer
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.forename: Mareike
authors.initials: M
authors.lastname: Wagner
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zeller
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D023201:CD40 Ligand / Q000172:deficiency / Q000276:immunology / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000187:drug effects / Q000502:physiology; D018858:Germinal Center / Q000166:cytology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology* / Q000235:genetics; D011328:Prions / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D021381:Protein Transport / Q000502:physiology
chemical_list: D000906:Antibodies; D005904:Glial Fibrillary Acidic Protein; D018620:PrPSc Proteins; D011328:Prions; D023201:CD40 Ligand