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November 1, 2005The Journal of ImmunologyOpen Access

The Murine B Cell Repertoire Is Severely Selected against Endogenous Cellular Prion Protein

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Key result

Endogenous PrPC expression profoundly affects the antibody repertoire, as B cells reactive for epitopes exposed on native PrPC are strongly tolerized in wild-type mice compared to Prnp o/o mice.

Population

Wild-type and PrP knockout (Prnp o/o) C57BL/6 mice

Comparison

Immunization with mouse PrP-plasmid DNA or with… vs Comparison between wild-type and Prnp o/o mice…

Design

Preclinical

Authors

SGSylvie GrégoireABAnne‐Sophie BergotCFCécile Feraudet‐Tarisse

Discussion

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Overview

Suggests caution for PrPC-targeted immunotherapies; leaves open translation from mouse tolerance data to human prion disease.

Structured PICO

P
Population
Wild-type and PrP knockout (Prnp o/o) C57BL/6 mice immunized with mouse PrP-plasmid DNA or overlapping peptides to assess antibody and T cell repertoires.
I
Intervention
Immunization with mouse PrP-plasmid DNA or with 30-mer overlapping peptides either emulsified in CFA or CpG/IFA
C
Comparator
Comparison between wild-type and Prnp o/o mice, and between different immunization adjuvants (CFA vs CpG/IFA)
O
Outcome
Antibody and T cell repertoires directed to PrP, including epitope recognition and antibody subclassessurrogate

Endogenous PrPC expression profoundly affects the antibody repertoire by strongly tolerizing B cells reactive to epitopes exposed on native PrPC, impacting potential immunotherapy strategies for prion diseases.

Cite This Study

Grégoire et al. (2005) studied Prion disease / immune response to PrP. Immunization with mouse PrP-plasmid DNA or 30-mer overlapping peptides vs. Wild-type vs Prnp o/o mice was evaluated on Antibody and T cell repertoires directed to PrP. Endogenous PrPC expression profoundly affects the antibody repertoire, as B cells reactive for epitopes exposed on native PrPC are strongly tolerized in wild-type mice compared to Prnp o/o mice.

synapsesocial.com/papers/6a93c30240aff459acebccafhttps://doi.org/10.4049/jimmunol.175.10.6443
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils2007 · 51 citations
  2. 2Polylactide-Coglycolide Microspheres CoEncapsulating Recombinant Tandem Prion Protein with CpG-Oligonucleotide Break Self-Tolerance to Prion Protein in Wild-Type Mice and Induce CD4 and CD8 T Cell Responses2007 · 55 citations
  3. 3Dendritic Cell-Mediated-Immunization with Xenogenic PrP and Adenoviral Vectors Breaks Tolerance and Prolongs Mice Survival against Experimental Scrapie2009 · 21 citations
  4. 4Electrotransfer of cDNA Coding for a Heterologous Prion Protein Generates Autoantibodies Against Native Murine Prion Protein in Wild-Type Mice2009 · 17 citations
  5. 5Protective anti‐prion antibodies in human immunoglobulin repertoires2020 · 25 citations