The murine B cell repertoire is severely selected against endogenous cellular prion protein

Gregoire, S, Bergot, AS, Feraudet, C, Carnaud, C, Aucouturier, P and Rosset, MB (2005) The murine B cell repertoire is severely selected against endogenous cellular prion protein. Journal of Immunology, 175 10: 6443-6449.

Author Gregoire, S
Bergot, AS
Feraudet, C
Carnaud, C
Aucouturier, P
Rosset, MB
Title The murine B cell repertoire is severely selected against endogenous cellular prion protein
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2005-11
Sub-type Article (original research)
Volume 175
Issue 10
Start page 6443
End page 6449
Total pages 7
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Abs to the prion protein (PrP) can protect against experimental prion infections, but efficient Ab responses are difficult to generate because PrP is expressed on many tissues and induces a strong tolerance. We previously showed that immunization of wild-type mice with PrP peptides and CpG oligodeoxynucleic acid overcomes tolerance and induces cellular and humoral responses to PrP. In this study, we compared Ab and T cell repertoires directed to PrP in wild-type and PrP knockout (Prnpo/o) C57BL/6 mice. Animals were immunized with mouse PrP-plasmid DNA or with 30-mer overlapping peptides either emulsified in CFA or CpG/IFA. In Prnpo/o mice, Abs raised by PrP-plasmid DNA immunization recognized only N-terminal PrP peptides; analyses of Ab responses after PrP peptide/CFA immunization allowed us to identify six distinct epitopes, five of which were also recognized by Abs raised by PrP peptides/CpG. By contrast, in wild-type mice, no Ab response was detected after PrP-plasmid DNA or peptide/CFA immunization. However, when using CpG, four C-terminal peptides induced Abs specific for distinct epitopes. Importantly, immune sera from Prnpo/o but not from wild-type mice bound cell surface PrP. Abs of IgG1 and IgG2b subclasses predominated in Prnpo/o mice while the strongest signals were for IgG2b in wild-type mice. Most anti-PrP Th cells were directed to a single epitope in both Prnpo/o and wild-type mice. We conclude that endogenous PrPC expression profoundly affects the Ab repertoire as B cells reactive for epitopes exposed on native PrPC are strongly tolerized. Implications for immunotherapy against prion diseases are discussed. Copyright © 2005 by The American Association of Immunologists, Inc.
Keyword Immunoglobulin Class Expression
Humoral Immune-Response
Cpg Motifs
Scrapie Agent
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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