Figure 1: Schematized Model of PrPSc Interactions in Lymph Nodes: 1. PrPSc is delivered to the lymph node in the afferent lymph. Free PrPSc may directly activate complement to assist in delivery, or may be phagocytosed and delivered by migratory dendritic cells. 2. PrPSc is targeted to the Follicular Dendritic Cells, probably through the interaction of complement degradation products on the PrPSc and CD21/CD35 on the surface of the FDC. 3. PrPSc may be amplified by converting PrPcon FDCs to PrPSc, or by secretion in the form of exosomes which are then phagocytosed by Tingible Body Macrophages in the germinal center. 4. B cells interact with the “infected” FDCs, potentially in an abortive attempt to respond to the conformationally foreign PrPSc. 5. Mature B cells downregulate CXCR5 and upregulate CXCR4, migrate from the germinal center to become either antibody secreting plasma cells or memory B cells that may have been infected with PrPSc. 6. PrPSc-containing memory B cells leave the lymph node in the efferent lymph where they re-enter the blood and home to germinal centers of distant lymphoid tissues via CXCR5 interactions