Pathogenesis of mouse scrapie: distribution of agent in the pulp and stroma of infected spleens.

Fourteen spleens were collected from mice infected with the 139A strain of scrapie, at a time when the concentration of agent in spleen was at a plateau. Scrapie infectivity was present in both the pulp and stromal fractions, but the concentration in stroma was about 10 times greater than that in pulp. On average, 1000 pulp cells were required to give 1 LD50 unit of scrapie infectivity. Linear regression analysis of data from 64 mouse spleens showed that the total infectivity correlated with tissue weight (P less than 0.001). The titres of the 14 stromal fractions were significantly correlated with whole spleen weight (P less than 0.02) and with the weight of stroma (P less than 0.02), but not with pulp weight. Hence, the titres in the isolated stroma probably reflect those of the stroma in vivo. In contrast, there was no correlation between total pulp titre and spleen weight, pulp weight or pulp cell number. Moreover, gentle washing of pulp cells removed about 80% of the total infectivity. This suggests that much of the pulp titre is adventitiously associated with cells and is in fact agent released from damaged stroma.