Cannabinoid receptor 2
endoplasmic reticulum
Regulation of Cell Surface CB<sub>2</sub> Receptor during Human B Cell Activation and Differentiation.
Cannabinoid receptor type 2 (CB<sub>2</sub>) is the primary receptor pathway mediating the immunologic consequences of cannabinoids. We recently reported that human peripheral blood B cells express CB<sub>2</sub> on both the extracellular membrane and at intracellular sites, where-as monocytes and T cells only express intracellular CB<sub>2</sub>. To better understand the pattern of CB<sub>2</sub> expression by human B cells, we examined CD20<sup>+</sup> 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<sup>+</sup>/CD38<sup>Dim</sup>). While naïve mature and quiescent memory B cells (IgD<sup>-</sup>/CD38<sup>-</sup>) from tonsils and peripheral blood exhibited a similar pattern, tonsillar activated B cells (IgD<sup>-</sup>/CD38<sup>+</sup>) expressed little to no surface CB<sub>2</sub>. We hypothesized that regulation of the surface CB<sub>2</sub> 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 CB<sub>2</sub> but express intracellular CB<sub>2</sub>. Furthermore, in vitro activation of human cord blood resulted in a down-regulation of surface CB<sub>2</sub> on those B cells acquiring the activated phenotype but not on those retaining IgD expression. Using a CB<sub>2</sub> expressing cell line (293 T/CB<sub>2</sub>-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 CB<sub>2</sub> in B cells that is specifically modulated during the course of B cell activation.