NR AQLH
AU McGovern,G.; Brown,K.L.; Bruce,M.E.; Jeffrey,M.J.
TI Murine scrapie infection causes an abnormal germinal centre reaction in the spleen
QU Journal of Comparative Pathology 2004 Feb-Apr; 130(2-3): 181-94
PT journal article
AB 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.
MH Animals; Antigen-Antibody Complex/immunology; Dendritic Cells, Follicular/immunology/pathology/ultrastructure; Germinal Center/*pathology/ultrastructure; Immunohistochemistry; Mice; Microscopy, Electron; Models, Immunological; PrPsc Proteins/*metabolism; Scrapie/*immunology/*pathology; Spleen/immunology/*pathology/ultrastructure
AD Gillian McGovern, Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK; K. L. Brown, M. E. Bruce, Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK
SP englisch
PO England