Germinal center B cells are dispensable in prion transport and neuroinvasion

Completed Research Project

Title / Titel: Germinal center B cells are dispensable in prion transport and neuroinvasion

Summary / Zusammenfassung: 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 effecting prion transport from lymphoreticular sites of replication to the nervous system.

Project Leadership and Contacts / Projektleitung und Kontakte

Prof. Dr. Adriano Aguzzi (Project Leader)	adriano.aguzzi@usz.ch
Dr. Mathias Heikenwälder, PhD	mathias.heikenwälder@usz.ch

Funding Source(s) / Unterstützt durch: Nachwuchsförderungskredit der Universität Zürich, Other Public Sources (e.g. Federal or Cantonal Agencies), Foundation