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rdf:type |
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lifeskim:mentions |
umls-concept:C0004561,
umls-concept:C0073337,
umls-concept:C0205147,
umls-concept:C0206071,
umls-concept:C0332257,
umls-concept:C0812385,
umls-concept:C1314939,
umls-concept:C1334087,
umls-concept:C1514873,
umls-concept:C1516349,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1710082,
umls-concept:C1879547
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pubmed:issue |
2
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pubmed:dateCreated |
2002-1-25
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pubmed:abstractText |
alpha 4 potentially mediates BCR signals through a rapamycin-sensitive TOR pathway. To investigate a potential role for alpha 4 in B cell activation, the alpha 4 gene was disrupted conditionally in B cells by mating male CD19-Cre mice with female alpha 4-floxed mice. CD19-Cre+/alpha 4flox mice showed loss of alpha 4 protein in B lineage cells and a decreased number of phenotypically normal mature B cells. Compared to normal B cells, alpha 4(-) B cells showed a decreased proliferation in response to the B cell stimulants (anti-IgM antibody plus IL-4, anti-CD40 mAb and lipopolysaccharide), and a reduced S6 kinase activation and rapamycin sensitivity. While CD19-Cre+/alpha 4flox mice showed impaired antibody responses to both T cell-independent and T cell-dependent (TD) antigens, the TD antigen response was markedly impaired as demonstrated by reduced isotype switching, reduced germinal center formation and reduced V region somatic hypermutation. These results show that alpha 4 plays a pivotal role in antigen-specific signal transduction during B cell activation and differentiation in vivo.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD19,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0953-8178
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
177-87
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11809737-Animals,
pubmed-meshheading:11809737-Antigens, CD,
pubmed-meshheading:11809737-Antigens, CD19,
pubmed-meshheading:11809737-B-Lymphocytes,
pubmed-meshheading:11809737-Enzyme Activation,
pubmed-meshheading:11809737-Female,
pubmed-meshheading:11809737-Immunoglobulin Class Switching,
pubmed-meshheading:11809737-Immunoglobulin Variable Region,
pubmed-meshheading:11809737-Integrin alpha4,
pubmed-meshheading:11809737-Lymphocyte Activation,
pubmed-meshheading:11809737-Male,
pubmed-meshheading:11809737-Mice,
pubmed-meshheading:11809737-Mice, Knockout,
pubmed-meshheading:11809737-Receptors, Antigen, B-Cell,
pubmed-meshheading:11809737-Ribosomal Protein S6 Kinases,
pubmed-meshheading:11809737-Signal Transduction,
pubmed-meshheading:11809737-Sirolimus,
pubmed-meshheading:11809737-Somatic Hypermutation, Immunoglobulin
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pubmed:year |
2002
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pubmed:articleTitle |
BCR signal through alpha 4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation.
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pubmed:affiliation |
Department of Immunology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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