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Across the globe, more than 39 million people are living with the Human Immunodeficiency Virus (HIV), the virus that causes AIDS, including more than 1.3 million new HIV diagnoses last year.
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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.
P2RY8 promotes the confinement and growth regulation of germinal center (GC) B cells, and loss of human P2RY8 is associated with B cell lymphomagenesis. The m