Relative Impact of Complement Receptors CD21/35 (Cr2/1) on Scrapie Pathogenesis in Mice

Area of Science:

• Immunology
• Neuroscience
• Prion Biology

Background:

• Complement receptors 1 and 2 (CR1/2 or CD35/CD21) are crucial for immune responses by recognizing complement-opsonized antigens.
• The mouse Cr2 gene generates alternatively spliced isoforms, CD35 and CD21, with distinct functions and expression patterns.
• Previous studies indicated that Cr2 depletion affects prion disease progression, but the specific roles of CD35 and CD21 were unclear.

Purpose of the Study:

• To investigate the distinct roles of CD35 and CD21 isoforms in prion disease pathogenesis.
• To determine whether CD35 or CD21 is more critical for prion replication and neuroinvasion.
• To elucidate the impact of CD21 deficiency on splenic architecture and prion accumulation.

Main Methods:

• Utilized mouse models with genetic deficiencies in CD21 or CD35.
• Quantified prion levels in spleens and brains at various time points post-infection.
• Assessed splenic follicular structure, including follicular dendritic cells (FDCs) and tingible body macrophages (TBMφs).

Main Results:

• Both CD35 and CD21 function as high-affinity cell surface prion receptors.
• Mice lacking CD21 exhibited significantly delayed terminal prion disease compared to CD35-deficient or wild-type mice.
• CD21-deficient mice showed reduced splenic prion loads early in infection and less organized follicular networks with fewer Mfge8-positive FDCs and TBMφs.

Conclusions:

• CD21 plays a more prominent role than CD35 in promoting efficient prion replication and accelerating prion disease.
• The impaired splenic architecture in CD21-deficient mice contributes to delayed prion neuroinvasion and disease progression.
• CD21 is critical for maintaining splenic follicular organization, which influences the pathogenesis of prion diseases.