Follicular dendritic cells in scrapie pathogenesis

Scrapie pathogenesis was studied in chimaeric mice that carried the prion p rotein (PrP) gene only in particular cells of the immune system. These mice were produced by grafting bone marrow from PrP expressing donors into PrP deficient recipients and vice versa. As follicular dendritic cells are not replaced significantly from the bone marrow in adult mice, this procedure r esulted in a mismatch in PrP genotype between these cells and bone marrow d erived cells such as lymphocytes. Using these models we obtained strong evi dence that follicular dendritic cells produced high levels of the normal fo rm of PrP in uninfected mice. Furthermore, the replication of a mouse-passa ged scrapie strain in the spleen depended only on the presence of PrP expre ssing follicular dendritic cells. PrP expression by lymphocytes or other bo ne marrow derived cells had no influence on replication in spleen or on neu roinvasion in these models. These results indicate that the follicular dend ritic cell is a potential target for prophylactic or therapeutic interventi on in transmissible spongiform encephalopathies.