Impaired prion replication in spleens of mice lacking functional follicular dendritic cells

In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes and in the stroma, which contains follicula r dendritic cells (FDCs), Formation and maintenance of mature FDCs require the presence of B cells expressing membrane-bound Lymphotoxin-alpha/beta. T reatment of mice with soluble lymphotoxin-beta receptor results in the disa ppearance of mature FDCs from the spleen. We show that this treatment aboli shes splenic prion accumulation and retards neuroinvasion after intraperito neal scrapie inoculation. These data provide evidence that FDCs are the pri ncipal sites for prion replication in the spleen.