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

Authors:
Top Cited Papers
Open Access
Publisher website
Google Scholar
Abstract
The environmental cues involved in regulating germinal center size are not fully understood. Cyster and colleagues show that the sphingosine 1-phosphate receptor S1P2 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 (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 Gα12, Gα13 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.

This publication has 51 references indexed in Scilit: