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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2011-6-20
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pubmed:abstractText |
Mice deficient in sphingosine 1-phosphate receptor type 2 (S1P(2)) develop diffuse large B cell lymphoma. However, the role of S1P(2) in normal germinal center (GC) physiology is unknown. Here we show that S1P(2)-deficient GC B cells outgrew their wild-type counterparts in chronically established GCs. We found that antagonism of the kinase Akt mediated by S1P(2) and its downstream mediators G?(12), G?(13) and p115RhoGEF regulated cell viability and was required for growth control in chronically proliferating GCs. Moreover, S1P(2) inhibited GC B cell responses to follicular chemoattractants and helped confine cells to the GC. In addition, S1P(2) overexpression promoted the centering of activated B cells in the follicle. We suggest that by inhibiting Akt activation and migration, S1P(2) helps restrict GC B cell survival and localization to an S1P-low niche at the follicle center.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1529-2916
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pubmed:author |
pubmed-author:AllenChristopher D CCD,
pubmed-author:ChoBryanB,
pubmed-author:CoughlinShaun RSR,
pubmed-author:CysterJason GJG,
pubmed-author:GreenJesse AJA,
pubmed-author:PalmerDanielD,
pubmed-author:ProiaRichard LRL,
pubmed-author:SchmidtTimothy HTH,
pubmed-author:SuzukiKazuhiroK,
pubmed-author:WillisonL DavidLD,
pubmed-author:XuYingY
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pubmed:issnType |
Electronic
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
672-80
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pubmed:dateRevised |
2011-10-28
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pubmed:meshHeading |
pubmed-meshheading:21642988-Animals,
pubmed-meshheading:21642988-B-Lymphocytes,
pubmed-meshheading:21642988-Cell Survival,
pubmed-meshheading:21642988-GTP-Binding Protein alpha Subunits, G12-G13,
pubmed-meshheading:21642988-Germinal Center,
pubmed-meshheading:21642988-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:21642988-Homeostasis,
pubmed-meshheading:21642988-Mice,
pubmed-meshheading:21642988-Mice, Inbred C57BL,
pubmed-meshheading:21642988-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21642988-Receptors, Lysosphingolipid
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pubmed:year |
2011
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pubmed:articleTitle |
The sphingosine 1-phosphate receptor S1P? maintains the homeostasis of germinal center B cells and promotes niche confinement.
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pubmed:affiliation |
Howard Hughes Medical Institute and Department of Microbiology and Immunology, San Francisco, California, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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