Source:http://linkedlifedata.com/resource/pubmed/id/16791898
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2006-8-7
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| pubmed:abstractText |
Mouse follicular B cells express TLR9 and respond vigorously to stimulation with single-stranded CpG-oligodeoxynucleotides (ODN). Surprisingly, follicular B cells do not respond to direct stimulation with other TLR9 ligands, such as bacterial DNA or class A(D) CpG-ODN capable of forming higher-order structures, unless other cell types are present. Here, we show that priming with interferons or with B cell-activating factor, or simultaneous co-engagement of the B cell receptor for antigen (BCR), can overcome this unresponsiveness. The effect of interferons occurs at the transcriptional level and is mediated through an autocrine/paracrine loop, which is dependent on IRF-1, IL-6 and IL-12 p40. We hypothesize that the lack of bystander activation of follicular B cells with more complex CpG ligands may be an important safety mechanism for avoiding autoimmunity. This will prevent resting B cells from responding to foreign or self-derived hypomethylated double-stranded CpG ligands unless these ligands are either delivered through the B cell receptor or under conditions where B cells are simultaneously co-engaged by activated plasmacytoid dendritic cells or TH1 cells. A corollary is that the heightened responsiveness of lupus B cells to TLR9-induced stimulation cannot be ascribed to unprimed follicular B cells, but is rather mediated by hypersensitive marginal zone B cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/CPG-oligonucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 9
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0014-2980
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
36
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1951-62
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16791898-Adjuvants, Immunologic,
pubmed-meshheading:16791898-Animals,
pubmed-meshheading:16791898-B-Lymphocytes,
pubmed-meshheading:16791898-CpG Islands,
pubmed-meshheading:16791898-DNA,
pubmed-meshheading:16791898-Disease Models, Animal,
pubmed-meshheading:16791898-Female,
pubmed-meshheading:16791898-Ligands,
pubmed-meshheading:16791898-Lupus Erythematosus, Systemic,
pubmed-meshheading:16791898-Lymphocyte Activation,
pubmed-meshheading:16791898-Mice,
pubmed-meshheading:16791898-Mice, Inbred BALB C,
pubmed-meshheading:16791898-Mice, Inbred C57BL,
pubmed-meshheading:16791898-Mice, Inbred DBA,
pubmed-meshheading:16791898-Mice, Inbred MRL lpr,
pubmed-meshheading:16791898-Mice, Inbred NZB,
pubmed-meshheading:16791898-Mice, Knockout,
pubmed-meshheading:16791898-Oligodeoxyribonucleotides,
pubmed-meshheading:16791898-Toll-Like Receptor 9
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| pubmed:year |
2006
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| pubmed:articleTitle |
Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice.
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| pubmed:affiliation |
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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