Michael A. Klein

TL;DR: It is found that scrapie developed after peripheral inoculation in mice expressing immunoglobulins that were exclusively of the M subclass and without detectable specificity for the normal form of thePrPc, and in mice which had differentiated B cells but no functional follicular dendritic cells.

TL;DR: It is shown that treatment of mice with soluble lymphotoxin-beta receptor abolishes splenic prion accumulation and retards neuroinvasion after intraperitoneal scrapie inoculation, providing evidence that FDCs are the principal sites for prion replication in the spleen.

TL;DR: The feasibility of immunological inhibition of prion disease in vivo is indicated by expressing an anti-prion protein (anti-PrP) μ chain in Prnp o/o mice and expression of endogenous PrP in the spleen and brain was unaffected, suggesting that immunity was responsible for protection.

TL;DR: Splenic accumulation of prion infectivity and PrPSc was delayed, indicating that activation of specific complement components is involved in the initial trapping of prions in lymphoreticular organs early after infection.

TL;DR: It is concluded that transfer of infectivity from the spleen to the central nervous system is crucially dependent on the expression of PrP in a tissue compartment that cannot be reconstituted by bone marrow transfer, and the requirement for the normal isoform of Prp in peripheral tissues represents a bottleneck for the spread of prions from peripheral sites to thecentral nervous system.