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. 2015 Dec 14;212(13):2213-22. doi: 10.1084/jem.20151250. Epub 2015 Nov 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Dendritic Cells, Follicular / metabolism*
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
  • Germinal Center / metabolism*
  • Humans
  • Lymph Nodes / metabolism
  • Mice, Inbred C57BL
  • Receptors, Lysosphingolipid / metabolism*
  • Receptors, Purinergic P2Y / metabolism*


  • P2RY8 protein, human
  • Receptors, Lysosphingolipid
  • Receptors, Purinergic P2Y
  • GTP-Binding Protein alpha Subunits, G12-G13