PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie‐infected mice

Abstract

Abnormal forms of a host protein, PrP, accumulate in the central nervous system in scrapie-affected animals. Here, PrP protein was detected immunocytochemically in tissue sections of spleen, lymph node, Peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of mouse-passaged scrapie strains and bovine spongiform encephalopathy (BSE). In the spleen, lymph node and Peyer's patches, PrP-positive cells were identified as follicular dendritic cells (FDC) by their location, appearance, and immune complex trapping function, whereas in the thymus they appeared to be two types of stromal cells: interdigitating cells (IDC) and cortical epithelial cells. In pancreas, PrP-containing cells were confined to the islets of Langerhans. Although the distribution of PrP immunolabelling was the same in tissues from scrapie-affected and uninfected mice, there was evidence that PrP accumulated in abnormal forms in FDC of infected mice. If, as is likely, PrP is essential for agent replication, our results suggest that FDC are the site of scrapie and BSE replication in the spleen and lymph node.

Immunologically Induced, Complement-Dependent Up-Regulation of the Prion Protein in the Mouse Spleen: Follicular Dendritic Cells Versus Capsule and Trabeculae

“…1). This was an unexpected finding because, to our knowledge, earlier reports on PrP in the spleen never mentioned a capsular or trabecular PrP expression pattern (5,8,11,17), although the present results show that the trabeculocapsular signal may normally be much more prominent than the well-established signal in the germinal center areas. Because the connective tissue structures of capsule and trabeculae are prone to unspecific staining, a series of experiments was performed to rule out any possibility of a staining artifact.…”

Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

“…6a). The cellular distribution of the PrP was consistent with accumulation in association with FDCs (6,44). After the early onset of accumulation, high levels of disease-specific PrP were sustained in Peyer's patches of control-treated mice through to the terminal stage of disease (data not shown).…”

“…Sections (6 m) were deparaffinized and pretreated to enhance PrP immunostaining by hydrated autoclaving (15 min, 121°C, hydration) and subsequent immersion in formic acid (98%) for 5 min (44). Sections were then stained with the PrPspecific polyclonal antiserum 1B3 (14) and immunolabeling was detected by using hydrogen peroxidase coupled to the avidin-biotin complex (Vector Laboratories) with diaminobenzidine as a substrate.…”

“…Within the lymphoid tissues of patients with vCJD (24), most sheep with natural scrapie (56), or after experimental peripheral inoculation of rodents with scrapie (6,28,37,39,44), early PrP Sc accumulation takes place in the germinal centre on follicular dendritic cells (FDCs). Studies of mouse scrapie models have shown that mature FDCs are critical for replication in lymphoid tissues and, in their absence, neuroinvasion after peripheral challenge is significantly impaired (6, 17, 31, 37-39, 46, 51).…”

Human FDC express PrPc invivo and invitro

“…Immunohistochemical staining with anti-PrP antibodies reveals an extraordinary accumulation of PrPres in the lymphoid follicles, especially in the form of a delicate network (Kitamoto et al, 1991;McBride et al, 1992;Klein et al, 1998;Jeffrey et al, 1999 extensions was intensely labelled (Fig. 1).…”