Document Detail


Phosphorothioate-modified CpG oligodeoxynucleotides mimic autoantigens and reveal a potential role for Toll-like receptor 9 in receptor revision.
MedLine Citation:
PMID:  23289794     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Re-expression of recombinase activating genes (RAG) in mature B cells may support autoreactivity by enabling revision of the B-cell receptor (BCR). Recent reports suggest that administration of Toll-like receptor 9 (TLR9) -stimulating CpG oligodeoxynucleotides (ODN) could trigger the manifestation of autoimmune disease and that TLR are involved in the selection processes eliminating autoreactive BCR. The mechanisms involved remain to be elucidated. This prompted us to ask, whether TLR9 could be involved in receptor revision. We found that phosphorothioate-modified CpG ODN (CpG(PTO)) induced expression of Ku70 and re-expression of RAG-1 in human peripheral blood B lymphocytes and Igλ expression in sorted Igκ(+) B cells. Further results revealed unselective binding specificity of CpG(PTO) -induced immunoglobulin and suggested that CpG(PTO) engage and/or mimic IgM receptor signalling, an important prerequisite for the initialization of receptor editing or revision. Altogether, our data describe a potential role for TLR9 in receptor revision and suggest that CpG(PTO) could mimic chromatin-bearing autoantigens by simultaneously engaging the BCR and TLR9 on IgM(+) B cells.
Authors:
Anne Doster; Saskia Ziegler; Sandra Foermer; Ralf Joachim Rieker; Klaus Heeg; Isabelle Bekeredjian-Ding
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-07-01     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  166-78     Citation Subset:  IM    
Copyright Information:
© 2013 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Nuclear / genetics,  immunology,  metabolism
Autoantigens / immunology*
B-Lymphocytes / drug effects,  immunology*,  metabolism
Blotting, Western
Cell Nucleus / immunology,  metabolism
Cells, Cultured
DNA-Binding Proteins / genetics,  immunology,  metabolism
Flow Cytometry
Homeodomain Proteins / genetics,  immunology,  metabolism
Humans
Immunoglobulin lambda-Chains / immunology,  metabolism
Interleukin-6 / immunology,  metabolism
Microscopy, Fluorescence
Oligodeoxyribonucleotides / immunology*,  pharmacology
Phosphorothioate Oligonucleotides / immunology,  pharmacology
Receptors, Antigen, B-Cell / immunology,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  immunology
Toll-Like Receptor 9 / agonists,  immunology*
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/Autoantigens; 0/CPG-oligonucleotide; 0/DNA-Binding Proteins; 0/Homeodomain Proteins; 0/Immunoglobulin lambda-Chains; 0/Interleukin-6; 0/Ku autoantigen; 0/Oligodeoxyribonucleotides; 0/Phosphorothioate Oligonucleotides; 0/Receptors, Antigen, B-Cell; 0/TLR9 protein, human; 0/Toll-Like Receptor 9; 128559-51-3/RAG-1 protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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