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

JR Muppidi, E Lu, JG Cyster - Journal of Experimental Medicine, 2015 - rupress.org
JR Muppidi, E Lu, JG Cyster
Journal of Experimental Medicine, 2015rupress.org
The orphan Gα13-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 Gα13-coupled receptor. Mutations in GNA13 and its downstream …
The orphan Gα13-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 Gα13-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 Gα13-dependent pathways, and they show that dissemination of Gα13-deficient GC B cells additionally requires an egress-promoting receptor.
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