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Mark D Zabel, Mathias Heikenwalder, Marco Prinz, Isabelle Arrighi, Petra Schwarz, Jan Kranich, Adriana von Teichman, Karen M Haas, Nicolas Zeller, Thomas F Tedder, John H Weis, Adriano Aguzzi, Stromal Complement Receptor CD21/35 Facilitates Lymphoid Prion Colonization and Pathogenesis, The Journal of Immunology, Volume 179, Issue 9, November 2007, Pages 6144–6152, https://doi.org/10.4049/jimmunol.179.9.6144
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Abstract
We have studied the role of CD21/35, which bind derivatives of complement factors C3 and C4, in extraneural prion replication and neuroinvasion. Upon administration of small prion inocula, CD21/35−/− mice experienced lower attack rates and delayed disease over both wild-type (WT) mice and mice with combined C3 and C4 deficiencies. Early after inoculation, CD21/35−/− spleens were devoid of infectivity. Reciprocal adoptive bone marrow transfers between WT and CD21/35−/− mice revealed that protection from prion infection resulted from ablation of stromal, but not hemopoietic, CD21/35. Further adoptive transfer experiments between WT mice and mice devoid of both the cellular prion protein PrPC and CD21/35 showed that splenic retention of inoculum depended on stromal CD21/35 expression. Because both PrPC and CD21/35 are highly expressed on follicular dendritic cells, CD21/35 appears to be involved in targeting prions to follicular dendritic cells and expediting neuroinvasion following peripheral exposure to prions.