First Author | Muppidi JR | Year | 2015 |
Journal | J Exp Med | Volume | 212 |
Issue | 13 | Pages | 2213-22 |
PubMed ID | 26573295 | Mgi Jnum | J:229019 |
Mgi Id | MGI:5750243 | Doi | 10.1084/jem.20151250 |
Citation | Muppidi JR, et al. (2015) The G protein-coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination. J Exp Med 212(13):2213-22 |
abstractText | The orphan Galpha13-coupled receptor P2RY8 is mutated in human germinal center (GC)-derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)-dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Galpha13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas. We find that egress of Gna13 mutant GC B cells from lymph nodes in the mouse depends on sphingosine-1-phosphate receptor-3. These findings provide evidence that FDCs promote GC confinement of both human and mouse GC B cells via Galpha13-dependent pathways, and they show that dissemination of Galpha13-deficient GC B cells additionally requires an egress-promoting receptor. |