title: The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, San Francisco, California, USA.
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Green
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Bryan
authors.initials: B
authors.lastname: Cho
authors.forename: L David
authors.initials: LD
authors.lastname: Willison
authors.forename: Daniel
authors.initials: D
authors.lastname: Palmer
authors.forename: Christopher D C
authors.initials: CD
authors.lastname: Allen
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Schmidt
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Shaun R
authors.initials: SR
authors.lastname: Coughlin
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000276:immunology*; D064067:Rho Guanine Nucleotide Exchange Factors
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D049349:Receptors, Lysosphingolipid; D064067:Rho Guanine Nucleotide Exchange Factors; D051057:Proto-Oncogene Proteins c-akt; D044365:GTP-Binding Protein alpha Subunits, G12-G13