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(American Journal of Pathology. 2003;162:1075-1081.)
© 2003 American Society for Investigative Pathology

CD21-Positive Follicular Dendritic Cells

A Possible Source of PrP^Sc in Lymph Node Macrophages of Scrapie-Infected Sheep

Lynn M. Herrmann^*, William P. Cheevers, William C. Davis, Donald P. Knowles^* and Katherine I. O’Rourke^*

Animal Disease Research Unit,^* Agricultural Research Service, U.S. Department of Agriculture, Pullman; and the Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington

Natural sheep scrapie is a prion disease characterized by the accumulation of PrP^Sc in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrP^Sc. In this study, lymph nodes were analyzed for the presence of PrP^Sc and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus-specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus-specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrP^Sc by phagocytosis of CD21+ FDC processes. The results also suggest that follicular macrophages have proteases that process full-length PrP^Sc to N-terminally truncated PrP^Sc.

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