Source:http://linkedlifedata.com/resource/pubmed/id/20623551
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2010-9-2
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| pubmed:abstractText |
B-cell receptor (BCR)-mediated signals provide the basis for B-cell differentiation in the BM and subsequently into follicular, marginal zone, or B-1 B-cell subsets. We have previously shown that B-cell-specific expression of the constitutive active E41K mutant of the BCR-associated molecule Bruton's tyrosine kinase (Btk) leads to an almost complete deletion of immature B cells in the BM. Here, we report that low-level expression of the E41K or E41K-Y223F Btk mutants was associated with reduced follicular B-cell numbers and significantly increased proportions of B-1 cells in the spleen. Crosses with 3-83 mu delta and VH81X BCR Tg mice showed that constitutive active Btk expression did not change follicular, marginal zone, or B-1 B-cell fate choice, but resulted in selective expansion or survival of B-1 cells. Residual B cells were hyperresponsive and manifested sustained Ca(2+) mobilization. They were spontaneously driven into germinal center-independent plasma cell differentiation, as evidenced by increased numbers of IgM(+) plasma cells in spleen and BM and significantly elevated serum IgM. Because anti-nucleosome autoantibodies and glomerular IgM deposition were present, we conclude that constitutive Btk activation causes defective B-cell tolerance, emphasizing that Btk signals are essential for appropriate regulation of B-cell activation.
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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/Agammaglobulinaemia tyrosine kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Antinuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Antigen-Antibody Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1521-4141
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
40
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2643-54
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| pubmed:dateRevised |
2011-11-2
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| pubmed:meshHeading |
pubmed-meshheading:20623551-Animals,
pubmed-meshheading:20623551-Antibodies, Antinuclear,
pubmed-meshheading:20623551-Antigen-Antibody Complex,
pubmed-meshheading:20623551-B-Lymphocyte Subsets,
pubmed-meshheading:20623551-Calcium Signaling,
pubmed-meshheading:20623551-Cell Differentiation,
pubmed-meshheading:20623551-Cell Proliferation,
pubmed-meshheading:20623551-Enzyme Activation,
pubmed-meshheading:20623551-Immune Tolerance,
pubmed-meshheading:20623551-Immunoglobulin M,
pubmed-meshheading:20623551-Lymphocyte Activation,
pubmed-meshheading:20623551-Mice,
pubmed-meshheading:20623551-Mice, Transgenic,
pubmed-meshheading:20623551-Mutant Proteins,
pubmed-meshheading:20623551-Plasma Cells,
pubmed-meshheading:20623551-Protein-Tyrosine Kinases,
pubmed-meshheading:20623551-Receptors, Antigen, B-Cell,
pubmed-meshheading:20623551-Transgenes
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| pubmed:year |
2010
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| pubmed:articleTitle |
Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells.
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| pubmed:affiliation |
Department of Immunology, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|