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Updated: Jul 10, 2026

Isolation of Murine Lymph Node Stromal Cells
Published on: August 19, 2014
Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis
Mark D Zabel1, Mathias Heikenwalder, Marco Prinz
1Institute for Neuropathology, University Hospital of Zürich, Zürich, Switzerland. mark.zabel@colostate.edu
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 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.
Insights
The complement receptor CD21/35 on stromal cells is crucial for prion replication and neuroinvasion. Ablating this receptor significantly delays prion disease by preventing splenic prion retention.
Area of Science:
- Immunology
- Neuroscience
- Infectious Diseases
Background:
- Prion diseases are fatal neurodegenerative disorders.
- Extraneural prion replication and neuroinvasion are key to disease pathogenesis.
- Complement receptors CD21/35 bind complement factors C3 and C4, implicated in immune responses.
Purpose of the Study:
- To investigate the role of CD21/35 in extraneural prion replication and neuroinvasion.
- To determine the cellular source of CD21/35 mediating prion susceptibility.
Main Methods:
- Utilized CD21/35 knockout (CD21/35(-/-)) mice and wild-type (WT) mice.
- Administered small prion inocula to assess disease progression and attack rates.
- Performed reciprocal adoptive bone marrow transfers to distinguish stromal vs. hemopoietic roles.
- Conducted further transfers with mice lacking both cellular prion protein (PrP(C)) and CD21/35.
Main Results:
- CD21/35(-/-) mice showed reduced attack rates and delayed prion disease onset compared to WT mice.
- Early splenic infectivity was absent in CD21/35(-/-) mice post-inoculation.
- Protection against prion infection was attributed to the absence of stromal CD21/35, not hemopoietic.
- Stromal CD21/35 expression was essential for splenic retention of prion inocula.
Conclusions:
- CD21/35 on follicular dendritic cells plays a critical role in prion targeting and neuroinvasion.
- Stromal CD21/35 mediates the initial splenic retention of prions following peripheral exposure.
- Targeting CD21/35 may offer a therapeutic strategy to prevent prion neuroinvasion.
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