Regulation of Cell Surface CB 2 Receptor during Human B Cell Activation and Differentiation

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+/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 cb2 receptor 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.