期刊
NATURE IMMUNOLOGY
卷 12, 期 7, 页码 672-U128出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2047
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资金
- National Science Foundation
- Howard Hughes Medical Institute
- US National Institutes of Health [HL65590, HL44907, AI45073]
- Grants-in-Aid for Scientific Research [23890097] Funding Source: KAKEN
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 alpha(12), Ga alpha(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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