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Updated: Aug 26, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Murine scrapie infection causes an abnormal germinal centre reaction in the spleen
G McGovern1, K L Brown, M E Bruce
1Veterinary Laboratories Agency Lasswade, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK.
Abstract:
Follicular dendritic cells (FDCs) of the lymphoreticular system play a role in the peripheral replication of prion proteins in some transmissible spongiform encephalopathies (TSEs), including experimental murine scrapie models. Disease-specific PrP (PrPd) accumulation occurs in association with the plasmalemma and extracellular space around FDC dendrites, but no specific immunological response has yet been reported in animals affected by TSEs. In the present study, morphology (light microscopical and ultrastructural) of secondary lymphoid follicles of the spleen were examined in mice infected with the ME7 strain of scrapie and in uninfected control mice, with or without immunological stimulation with sheep red blood cells (SRBCs), at 70 days post-inoculation or at the terminal stage of disease (268 days). Scrapie infection was associated with hypertrophy of FDC dendrites, increased retention of electron-dense material at the FDC plasma membrane, and increased maturation and numbers of B lymphocytes within secondary follicles. FDC hypertrophy was particularly conspicuous in immune-stimulated ME7-infected mice. The electron-dense material was associated with PrP Napoli accumulation, as determined by immunogold labelling. We hypothesize that immune system changes are associated with increased immune complex trapping by hypertrophic FDCs expressing PrP Napoli molecules at the plasmalemma of dendrites, and that this process is exaggerated by immune system stimulation. Contrary to previous dogma, these results show that a pathological response within the immune system follows scrapie infection.
Insights
Follicular dendritic cells (FDCs) in scrapie-infected mice show significant changes, including enlarged dendrites and increased prion protein accumulation. Immune stimulation exacerbates these effects, indicating a pathological immune response.
Area of Science:
- Immunology
- Neuroscience
- Pathology
Background:
- Follicular dendritic cells (FDCs) are implicated in prion protein replication in transmissible spongiform encephalopathies (TSEs).
- Prion disease (PrPd) accumulation occurs around FDCs, but a specific immune response has not been identified.
- Scrapie models provide a platform to study FDC roles in prion diseases.
Purpose of the Study:
- To investigate the morphological changes in FDCs and B lymphocytes in scrapie-infected mice.
- To determine the effect of immune stimulation on FDC morphology and prion accumulation.
- To identify a pathological immune response in the spleen during scrapie infection.
Main Methods:
- Comparative analysis of spleen secondary lymphoid follicles from scrapie-infected and control mice.
- Light and ultrastructural microscopy to assess FDC and B lymphocyte morphology.
- Immunogold labeling to detect PrP Napoli accumulation.
- Immune stimulation using sheep red blood cells (SRBCs).
Main Results:
- Scrapie infection led to FDC dendrite hypertrophy and increased retention of electron-dense material at the FDC plasma membrane.
- Increased B lymphocyte maturation and numbers were observed in secondary follicles of infected mice.
- FDC hypertrophy and prion accumulation were more pronounced in immune-stimulated, scrapie-infected mice.
Conclusions:
- Scrapie infection induces significant pathological changes in FDCs and associated B lymphocytes.
- Immune stimulation amplifies FDC hypertrophy and prion accumulation, suggesting a role for immune complexes.
- These findings demonstrate a pathological immune response within the immune system following scrapie infection, challenging previous assumptions.
