The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.
Copyright policy )The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.
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.
- National Institute of Diabetes and Digestive and Kidney Diseases United States
- National Institutes of Health United States
- National Institute of Health Pakistan
- University of California, San Francisco United States
- University of California San Francisco United States
Mice, Inbred C57BL, B-Lymphocytes, Mice, Receptors, Lysosphingolipid, Cell Survival, Animals, Guanine Nucleotide Exchange Factors, Homeostasis, Germinal Center, GTP-Binding Protein alpha Subunits, G12-G13, Proto-Oncogene Proteins c-akt, Rho Guanine Nucleotide Exchange Factors
Mice, Inbred C57BL, B-Lymphocytes, Mice, Receptors, Lysosphingolipid, Cell Survival, Animals, Guanine Nucleotide Exchange Factors, Homeostasis, Germinal Center, GTP-Binding Protein alpha Subunits, G12-G13, Proto-Oncogene Proteins c-akt, Rho Guanine Nucleotide Exchange Factors
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