The G Protein-coupled Receptor P2RY8 and Follicular Dendritic Cells Promote Germinal Center Confinement of B Cells, Whereas S1PR3 Can Contribute to Their Dissemination

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2015 Nov 18

PMID 26573295

Citations 37

Authors

Jagan R Muppidi

Erick Lu

Jason G Cyster

Affiliations

Soon will be listed here.

Abstract

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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References

Sehn L, Scott D, Chhanabhai M, Berry B, Ruskova A, Berkahn L . Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2011; 29(11):1452-7. DOI: 10.1200/JCO.2010.33.3419. View

Crotty S . Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011; 29:621-63. DOI: 10.1146/annurev-immunol-031210-101400. View

Morin R, Mendez-Lago M, Mungall A, Goya R, Mungall K, Corbett R . Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011; 476(7360):298-303. PMC: 3210554. DOI: 10.1038/nature10351. View

Yagi H, Tan W, Dillenburg-Pilla P, Armando S, Amornphimoltham P, Simaan M . A synthetic biology approach reveals a CXCR4-G13-Rho signaling axis driving transendothelial migration of metastatic breast cancer cells. Sci Signal. 2011; 4(191):ra60. PMC: 3429372. DOI: 10.1126/scisignal.2002221. View

Wang X, Cho B, Suzuki K, Xu Y, Green J, An J . Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers. J Exp Med. 2011; 208(12):2497-510. PMC: 3256970. DOI: 10.1084/jem.20111449. View

Lohr J, Stojanov P, Lawrence M, Auclair D, Chapuy B, Sougnez C . Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012; 109(10):3879-84. PMC: 3309757. DOI: 10.1073/pnas.1121343109. View

Cyster J, Schwab S . Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu Rev Immunol. 2011; 30:69-94. DOI: 10.1146/annurev-immunol-020711-075011. View

Victora G, Nussenzweig M . Germinal centers. Annu Rev Immunol. 2012; 30:429-57. DOI: 10.1146/annurev-immunol-020711-075032. View

Victora G, Dominguez-Sola D, Holmes A, Deroubaix S, Dalla-Favera R, Nussenzweig M . Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas. Blood. 2012; 120(11):2240-8. PMC: 3447782. DOI: 10.1182/blood-2012-03-415380. View

10.

Yi T, Wang X, Kelly L, An J, Xu Y, Sailer A . Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses. Immunity. 2012; 37(3):535-48. PMC: 3465460. DOI: 10.1016/j.immuni.2012.06.015. View

11.

Schmitz R, Young R, Ceribelli M, Jhavar S, Xiao W, Zhang M . Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012; 490(7418):116-20. PMC: 3609867. DOI: 10.1038/nature11378. View

12.

Meechan D, Tucker E, Maynard T, LaMantia A . Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome. Proc Natl Acad Sci U S A. 2012; 109(45):18601-6. PMC: 3494945. DOI: 10.1073/pnas.1211507109. View

13.

Bannard O, Horton R, Allen C, An J, Nagasawa T, Cyster J . Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection. Immunity. 2013; 39(5):912-24. PMC: 3828484. DOI: 10.1016/j.immuni.2013.08.038. View

14.

Jarjour M, Jorquera A, Mondor I, Wienert S, Narang P, Coles M . Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells. J Exp Med. 2014; 211(6):1109-22. PMC: 4042641. DOI: 10.1084/jem.20132409. View

15.

Moriyama S, Takahashi N, Green J, Hori S, Kubo M, Cyster J . Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers. J Exp Med. 2014; 211(7):1297-305. PMC: 4076581. DOI: 10.1084/jem.20131666. View

16.

Muppidi J, Schmitz R, Green J, Xiao W, Larsen A, Braun S . Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature. 2014; 516(7530):254-8. PMC: 4267955. DOI: 10.1038/nature13765. View

17.

McDermott D, Gao J, Liu Q, Siwicki M, Martens C, Jacobs P . Chromothriptic cure of WHIM syndrome. Cell. 2015; 160(4):686-699. PMC: 4329071. DOI: 10.1016/j.cell.2015.01.014. View

18.

Matloubian M, Lo C, Cinamon G, Lesneski M, Xu Y, Brinkmann V . Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004; 427(6972):355-60. DOI: 10.1038/nature02284. View

19.

Ansel K, Ngo V, Hyman P, Luther S, Forster R, Sedgwick J . A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 2000; 406(6793):309-14. DOI: 10.1038/35018581. View

20.

Suan D, Nguyen A, Moran I, Bourne K, Hermes J, Arshi M . T follicular helper cells have distinct modes of migration and molecular signatures in naive and memory immune responses. Immunity. 2015; 42(4):704-18. DOI: 10.1016/j.immuni.2015.03.002. View