PMID:28364261

Citation	'Castaneda, JT, Harui, A and Roth, MD (2017) Regulation of Cell Surface CB2 Receptor during Human B Cell Activation and Differentiation. J Neuroimmune Pharmacol '
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 CB2 on both the extracellular membrane and at intracellular sites, where-as monocytes and T cells only express intracellular CB2. To better understand the pattern of CB2 expression 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(+)/CD38(Dim)). 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 CB2 receptor 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 CB2 but express intracellular CB2. Furthermore, in vitro activation of human cord blood resulted in a down-regulation of surface CB2 on those B cells acquiring the activated phenotype but not on those retaining IgD expression. Using a CB2 expressing 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 CB2 in B cells that is specifically modulated during the course of B cell activation.
Links	PubMed Online version:10.1007/s11481-017-9744-7
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CNR2		GO:0005783: endoplasmic reticulum	ECO:0000314:		C		HUMAN CNR2 (CB2) // “Extensive co-localization of fluorescent images was observed when dual staining for ER and CB2 was carried out in cells from the 293 T/CB2-GFP line and imaged by confocal microscopy. An identical pattern of co-localization was also observed between the CB2 receptor and ER staining, but not CB2 and mitochondrial staining, in the SUDHL-4 cell line (data not shown).” (Fig 5C).	complete CACAO 12694

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