Research ArticleLYMPHOCYTE MIGRATION

Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione

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Science Immunology  04 Jun 2021:
Vol. 6, Issue 60, eabg1101
DOI: 10.1126/sciimmunol.abg1101

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A bouncer for the bone marrow

P2RY8 is a G protein–coupled receptor (GPCR) that is involved in restraining germinal center (GC) B cell migration and growth. It is unclear how the ligand of P2RY8, S-geranylgeranyl-l-glutathione (GGG), is involved in these processes. Using gain-of-function mouse models and genetically modified human T cells, Gallman et al. showed that expression of gamma-glutamyltransferase-5 (Ggt5) on stromal cells and ATP-binding cassette subfamily C member 1 (Abcc1) on hematopoietic cells was involved in catabolizing and transporting GGG, respectively, and restraining P2RY8+ cells within GCs. GGG and P2RY8 interactions also restrained lymphocyte trafficking to the bone marrow. Thus, GGG and P2RY8 processing and interactions are crucial for the confinement of B cells within GCs and for inhibiting migration of lymphocytes into bone marrow.

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