Heikenwaelder
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Heikenwaelder
Completed research project
| Title / Titel | The role of functional germinal center B-cells in prion pathogenesis | ||||||||
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| Abstract (PDF, 14 KB) | |||||||||
| Summary / Zusammenfassung | Prion diseases are fatal neurodegenerative disorders affecting both humans and animals. In contrast to other neurodegenerative diseases (e.g. Parkinson, Alzheimer¡≈s) prion diseases are transmissible. The mechanism of prion transmission is ill understood and subject to intense research. Under particular scrutiny is the role of the Lymphoreticular system in particular the function of follicular dendritic cells (FDCs) in the process of neuroinvasion. In spite of strong evidence suggesting a critical role of FDCs for the pathogenesis, definitive proof is still lacking as exclusive depletion of that cell type in vivo has not yet been achieved. Depletion of FDCs using antagonists of LT£]-Receptor signaling (LTƒÒR-Fc) also results in disruption of B cell follicles. Thus an exclusive role for FDCs independent of B cell function has not yet been established. Goal of our study is to deplete B cell follicles while maintaining normal FDC-networks. Blocking the engagement of the co-receptor CD40 on B cells by administration of the CD40-L antibody ablates the germinal center reaction, leading to ¡§non-functional¡¨ B-cell follicles without affecting the survival of FDCs, as shown on immunohistochemical level. Upon inoculation of prion protein, peripheral prion replication as well as its impact on neuroinvasion will be assessed. This approach will shed light onto the role of germinal center B cell-FDC interactions, B cell activation and germinal centers during prion pathogenesis. | ||||||||
| Keywords / Suchbegriffe | CD40-L antibody, FDCs, germinal centers, PrPSC | ||||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.uzh.ch/pathol/neuropathologie/d/index.html | ||||||||
| Funding source(s) / Unterstützt durch |
Others Catello Family |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Apr 2003 to Mar 2006 |