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

Abstract

The expression of the prion protein (PrP) in the follicular dendritic cell network of germinal centers in the spleen is critical for the splenic propagation of the causative agent of prion diseases. However, a physiological role of the prion protein in the periphery remains elusive. To investigate the role and function of PrP expression in the lymphoid system we treated naive mice i.v. with preformed immune complexes or vesicular stomatitis virus. Immunohistochemistry and Western blot analysis of the spleen revealed that 8 days after immunization, immune complexes and vesicular stomatitis virus had both induced a strong increase of PrP expression in the follicular dendritic cell network. Remarkably, this up-regulation did not occur in mice that lack an early factor of the complement cascade, C1q, a component which has been shown previously to facilitate early prion pathogenesis. In addition to the variable PrP level in the germinal centers, we detected steady and abundant PrP expression in the splenic capsule and trabeculae, which are structural elements that have not been associated before with PrP localization. The abundant trabeculo-capsular PrP expression was also evident in spleens of Rag-1-deficient mice, which have been shown before to be incapable of prion expansion. We conclude that trabeculocapsular PrP is not sufficient for splenic prion propagation. Furthermore, our observations may provide important clues for a physiological function of the prion protein and allow a new view on the role of complement and PrP in peripheral prion pathogenesis.

Resistance of Neonatal Mice to Scrapie Is Associated with Inefficient Infection of the Immature Spleen

“…4). From 10 days onward, PrP c labeling was also seen in the spleen capsule and trabeculae, as has been reported previously for adult mice (32). No labeling was seen in control spleen sections from age-matched PrP-deficient mice or in control spleen sections from PrP-expressing mice where the PrP-specific antibody had been replaced with normal rabbit serum (not shown).…”

Lymphoid signal transduction mechanisms linked to cellular prion protein

“…Cashman and colleagues (1990) have reported that in peripheral lymphoid cells polyclonal antibodies directed against PrP C can inhibit lectin-induced activation of human T cells, and this was recently confirmed in a similar system using monoclonal antibodies ). PrP C expression in mouse splenocytes has been widely documented, and despite the fact that these splenocytes possess much less PrP C surface immunoreactivity than human lymphocytes (Holada and Vostal 2000;Liu et al 2001;Parizek et al 2001;Lötscher et al 2003), splenocytes derived from PrP 0/ 0 129/Ola mice show decreased proliferation following lectin treatment (Mabbott et al 1997). The low level of expression we observe in spleen cells is consistent with previous reports (Mabbott et al 1997;Holada and Vostal 2000;Liu et al 2001;Parizek et al 2001;Lötscher et al 2003).…”

The Effects of Host Age on the Transport of Complement-Bound Complexes to the Spleen and the Pathogenesis of Intravenous Scrapie Infection

“…The aging-related factors responsible for the downregulation of PrP C expression by FDCs are uncertain. Data suggest that PrP C expression by FDCs is upregulated by immune complex trapping (29). In the absence of complement component C1q, the upregulation of PrP C could not be provoked.…”