PrP expression in B lymphocytes is not required for prion neuroinvasion

Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy, new variant Creutzfeldt-J akob disease(1), kuru and most cases of iatrogenic Creutzfeldt-Jakob diseas e. In mouse scrapie, prion infectivity accumulates in lymphoid organs, and the absence of mature B lymphocytes prevents peripherally administered prio ns from inducing central nervous system disease(2). We have now assessed wh ether expression of the cellular prion protein, PrPc, is required for B lym phocytes to mediate neuroinvasion. We found that repopulation of SCID and R ag-1(-/-) mice with fetal liver cells from either PrP-expressing or PrP-def icient mice and from T-cell deficient mice, but not from B-cell deficient m ice, is equally efficient in restoring neuroinvasion after intraperitoneal inoculation of scrapie prions. These results indicate that cells whose matu ration depends on B cells or their products, such as follicular dendritic c ells, may enhance neuroinvasion. Alternatively, B cells may transport prion s to the nervous system by a PrP-independent mechanism.