Cellular and sub-cellular localisation of PrP in the lymphoreticular system of mice and sheep

Using immunocytochemistry or immunogold electron microscopy, abnormal PrP a ccumulation was found in lymphoreticular tissues of Suffolk sheep naturally exposed to scrapie and in the spleens of ME7 infected C57 BL mice at 70 da ys after infection and at the terminal stage of disease at 170 days. Clinic ally diseased scrapie affected sheep show widespread PrP accumulation withi n tingible body macrophages (TBMs) and follicular dendritic cells (FDCs) of secondary lymphoid follicles. Serial tonsillar biopsies taken from 171ARQ/ ARQ sheep at 4 months of age did not contain abnormal PrP accumulations but 80% of biopsies were positive by 14 months. In contrast? whole body necrop sies of sheep not previously biopsied failed to detect PrP in the tonsil of sheep at 4, 8, 12 or 16 months of age. These findings suggest that the bio psy procedure of susceptible sheep but not resistant sheep may induce tonsi llar infection. In spleen of mice both at 70 and 170 dpi, accumulations of PrP were found within lysosomes of TBMs and also at the plasma-lemma of FDC s. In the light zone of follicles of terminally diseased mice, all FDC dend rites were arranged in the form of highly reactive or hyperplastic labrynth ine glomerular complexes. PrP was consistently seen between FDC dendrites i n association with abundant electron dense antigen-antibody complexes. At 7 0 days after challenge, labrynthine complexes were rare and invariably labe lled for PrP. However, sparse PrP labelling was also seen on simple FDC den drites at this stage. These observations suggests that scrapie infected FDC s continually release PrP from the cell surface where it accumulates in exc ess in association with trapped immune complexes and dendritic extension. I t is likely that TBMs acquire lysosomal PrP following phagocytosis of effet e FDC processes or from the extracellular space. We suggest that the normal function of PrP may involve cell process extension or immune complex trapp ing.