title: Regulation of Cell Surface CB2Receptor during Human B Cell Activation and Differentiation.
abstract: Cannabinoid receptor type 2 (CB2) is the primary receptor pathway mediating the immunologic consequences of cannabinoids. We recently reported that human peripheral blood B cells express CB2on both the extracellular membrane and at intracellular sites, where-as monocytes and T cells only express intracellular CB2. To better understand the pattern of CB2expression by human B cells, we examined CD20+B cells from three tissue sources. Both surface and intracellular expression were present and uniform in cord blood B cells, where all cells exhibited a naïve mature phenotype (IgD+/CD38Dim). While naïve mature and quiescent memory B cells (IgD-/CD38-) from tonsils and peripheral blood exhibited a similar pattern, tonsillar activated B cells (IgD-/CD38+) expressed little to no surface CB2. We hypothesized that regulation of the surface CB2receptor may occur during B cell activation. Consistent with this, a B cell lymphoma cell line known to exhibit an activated phenotype (SUDHL-4) was found to lack cell surface CB2but express intracellular CB2. Furthermore, in vitro activation of human cord blood resulted in a down-regulation of surface CB2on those B cells acquiring the activated phenotype but not on those retaining IgD expression. Using a CB2expressing cell line (293 T/CB2-GFP), confocal microscopy confirmed the presence of both cell surface expression and multifocal intracellular expression, the latter of which co-localized with endoplasmic reticulum but not with mitochondria, lysosomes, or nucleus. Our findings suggest a dynamic multi-compartment expression pattern for CB2in B cells that is specifically modulated during the course of B cell activation.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, CHS 37-131, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1690, USA.|Inter-Departmental Program in Molecular Toxicology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Julie T
authors.initials: JT
authors.lastname: Castaneda
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, CHS 37-131, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1690, USA.
authors.forename: Airi
authors.initials: A
authors.lastname: Harui
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, CHS 37-131, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1690, USA. mroth@mednet.ucla.edu.|Inter-Departmental Program in Molecular Toxicology, University of California, Los Angeles, Los Angeles, CA, 90095, USA. mroth@mednet.ucla.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis*
chemical_list: C588309:CNR2 protein, human; D043885:Receptor, Cannabinoid, CB2
keywords: B cell activation; B cells; Cannabinoid receptor CB2; Cannabinoids; G protein-coupled receptors; Intracellular membrane receptors