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- Title
The sphingosine 1-phosphate receptor S1P<sub>2</sub> maintains the homeostasis of germinal center B cells and promotes niche confinement.
- Authors
Green, Jesse A; Suzuki, Kazuhiro; Cho, Bryan; Willison, L David; Palmer, Daniel; Allen, Christopher D C; Schmidt, Timothy H; Xu, Ying; Proia, Richard L; Coughlin, Shaun R; Cyster, Jason G
- Abstract
Mice deficient in sphingosine 1-phosphate receptor type 2 (S1P2) develop diffuse large B cell lymphoma. However, the role of S1P2 in normal germinal center (GC) physiology is unknown. Here we show that S1P2-deficient GC B cells outgrew their wild-type counterparts in chronically established GCs. We found that antagonism of the kinase Akt mediated by S1P2 and its downstream mediators G?12, G?13 and p115RhoGEF regulated cell viability and was required for growth control in chronically proliferating GCs. Moreover, S1P2 inhibited GC B cell responses to follicular chemoattractants and helped confine cells to the GC. In addition, S1P2 overexpression promoted the centering of activated B cells in the follicle. We suggest that by inhibiting Akt activation and migration, S1P2 helps restrict GC B cell survival and localization to an S1P-low niche at the follicle center.
- Publication
Nature Immunology, 2011, Vol 12, Issue 7, p672
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni.2047