The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.

TitleThe sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.
Publication TypeJournal Article
Year of Publication2011
AuthorsGreen JA, Suzuki K, Cho B, L Willison D, Palmer D, Allen CDC, Schmidt TH, Xu Y, Proia RL, Coughlin SR, Cyster JG
JournalNat Immunol
Volume12
Issue7
Pagination672-80
Date Published2011 Jun 05
ISSN1529-2916
KeywordsAnimals, B-Lymphocytes, Cell Survival, Germinal Center, GTP-Binding Protein alpha Subunits, G12-G13, Guanine Nucleotide Exchange Factors, Homeostasis, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins c-akt, Receptors, Lysosphingolipid, Rho Guanine Nucleotide Exchange Factors
Abstract

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 Gα(12), Gα(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.

DOI10.1038/ni.2047
Alternate JournalNat. Immunol.
PubMed ID21642988
PubMed Central IDPMC3158008
Grant ListR01 HL044907 / HL / NHLBI NIH HHS / United States
HL65590 / HL / NHLBI NIH HHS / United States
HHMI_CYSTER_J / / Howard Hughes Medical Institute / United States
R01 AI045073-10 / AI / NIAID NIH HHS / United States
R01 AI045073 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States
R01 HL065590 / HL / NHLBI NIH HHS / United States
HL44907 / HL / NHLBI NIH HHS / United States
AI45073 / AI / NIAID NIH HHS / United States