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

Abstract

Sphingosine-1-phosphate receptor-2 (S1P2)-deficient mice 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 outgrow their wild-type counterparts in chronically-established GCs. We find that S1P2-, G12–G13- and p115RhoGEF-mediated antagonism of Akt regulates cell viability and is required for growth control in chronically proliferating GCs. We also find that S1P2 inhibits GC B cell responses to follicular chemoattractants and helps confine cells to the GC. Moreover, S1P2 overexpression promotes centering of activated B cells within 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.