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

The environmental cues involved in regulating germinal center size are not fully understood. Cyster and colleagues show that the sphingosine 1-phosphate receptor S1P 2 controls the survival and localization of B cells in germinal centers by antagonizing signaling by the kinase Akt and follicular chemoattractants. 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.