Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis.

Published

Journal Article

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 PrP(C) and CD21/35 showed that splenic retention of inoculum depended on stromal CD21/35 expression. Because both PrP(C) 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.

Full Text

Duke Authors

Cited Authors

  • Zabel, MD; Heikenwalder, M; Prinz, M; Arrighi, I; Schwarz, P; Kranich, J; von Teichman, A; Haas, KM; Zeller, N; Tedder, TF; Weis, JH; Aguzzi, A

Published Date

  • November 1, 2007

Published In

Volume / Issue

  • 179 / 9

Start / End Page

  • 6144 - 6152

PubMed ID

  • 17947689

Pubmed Central ID

  • 17947689

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.179.9.6144

Language

  • eng

Conference Location

  • United States