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PTO-modified CpG oligodeoxynucleotides mimic autoantigens and reveal a potential role for TLR9 in receptor revision.
MedLine Citation:
PMID:  23289794     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Re-expression of 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 (TLR)-9-stimulating CpG oligodeoxynucleotides (ODN) could trigger 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 signaling, 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. © 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
Authors:
Anne Doster; Saskia Ziegler; Sandra Foermer; Ralf Joachim Rieker; Klaus Heeg; Isabelle Bekeredjian-Ding
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-5
Journal Detail:
Title:  Immunology     Volume:  -     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
Affiliation:
Department of Infectious Diseases, Med. Microbiology and Hygiene, UniversityHospital Heidelberg, Im Neuenheimer Feld 324 1, OG, D-69120, Heidelberg, Germany.
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