The G protein-coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination.

ABSTRACT: The orphan G?13-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 G?13-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 G?13-dependent pathways, and they show that dissemination of G?13-deficient GC B cells additionally requires an egress-promoting receptor.

SUBMITTER: Muppidi JR 

PROVIDER: S-EPMC4689170 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature