rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-11-16
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pubmed:abstractText |
To identify genes and mechanisms involved in humoral immunity, we did a mouse genetic screen for mutations that do not affect the first wave of antibody to immunization but disrupt response maturation and persistence. The first two mutants identified had loss-of-function mutations in the gene encoding a previously obscure member of a family of Rho-Rac GTP-exchange factors, DOCK8. DOCK8-mutant B cells were unable to form marginal zone B cells or to persist in germinal centers and undergo affinity maturation. Dock8 mutations disrupted accumulation of the integrin ligand ICAM-1 in the B cell immunological synapse but did not alter other aspects of B cell antigen receptor signaling. Humoral immunodeficiency due to Dock8 mutation provides evidence that organization of the immunological synapse is critical for signaling the survival of B cell subsets required for long-lasting immunity.
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pubmed:grant |
|
pubmed:commentsCorrections |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
1529-2916
|
pubmed:author |
pubmed-author:AlstonDuncanD,
pubmed-author:BatistaFacundo DFD,
pubmed-author:Bouriez-JonesTiphaineT,
pubmed-author:BrinkRobertR,
pubmed-author:CamidgeTahraT,
pubmed-author:ChanTyani DTD,
pubmed-author:CornallRichard JRJ,
pubmed-author:CrockfordTanya LTL,
pubmed-author:CysterJason GJG,
pubmed-author:DeenickElissa KEK,
pubmed-author:DomaschenzHeatherH,
pubmed-author:EndersAnselmA,
pubmed-author:GoodnowChristopher CCC,
pubmed-author:JohnsonAndy LAL,
pubmed-author:JohnsonAndyA,
pubmed-author:KucharskaEdytaE,
pubmed-author:LambeTeresaT,
pubmed-author:LenardoMichael JMJ,
pubmed-author:MackayFabienneF,
pubmed-author:RandallKatrina LKL,
pubmed-author:TangyeStuart GSG,
pubmed-author:TreanorBebhinnB,
pubmed-author:TzeLina ELE,
pubmed-author:VinuesaCarola GCG,
pubmed-author:WhittleBelindaB
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pubmed:issnType |
Electronic
|
pubmed:volume |
10
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1283-91
|
pubmed:dateRevised |
2010-6-22
|
pubmed:meshHeading |
pubmed-meshheading:19898472-Amino Acid Sequence,
pubmed-meshheading:19898472-Animals,
pubmed-meshheading:19898472-Antibody Formation,
pubmed-meshheading:19898472-B-Lymphocytes,
pubmed-meshheading:19898472-Base Sequence,
pubmed-meshheading:19898472-Germinal Center,
pubmed-meshheading:19898472-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:19898472-Humans,
pubmed-meshheading:19898472-Lymphocyte Activation,
pubmed-meshheading:19898472-Mice,
pubmed-meshheading:19898472-Mice, Inbred C57BL,
pubmed-meshheading:19898472-Models, Molecular,
pubmed-meshheading:19898472-Molecular Sequence Data,
pubmed-meshheading:19898472-Mutation,
pubmed-meshheading:19898472-Protein Structure, Quaternary,
pubmed-meshheading:19898472-Sequence Alignment,
pubmed-meshheading:19898472-Synapses
|
pubmed:year |
2009
|
pubmed:articleTitle |
Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production.
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pubmed:affiliation |
John Curtin School of Medical Research and Australian Phenomics Facility, Australian National University, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|