Nearly all immune cells express cannabinoid receptors, with B cells having the highest levels of expression, followed by natural killer cells, polymorphonuclear neutrophils, T8 cells, monocytes, and T4 cells. AEA has long been known to act as a hematopoietic stem cell growth factor via CB2 in cooperation with other known growth factors such as IL-3, erythropoietin, and granulocyte colony-stimulating factor. THC stimulates lymphocytic production of TGF-beta via CB2 activation, and this appears to be the mechanism by which CB2 regulates itself via a negative autocrine loop. In the innate immune system, the ECS generally has an anti-inflammatory effect; however, 2-AG appears to have a more inflammatory role as it is broken down more readily to arachidonic acid and can stimulate macrophages to increase phagocytosis via CB2. In the adaptive immune system, T-cell populations are limited by activation of both PPAR-gamma and CB2. Activation of CB2 receptor has been shown to shift the balance of TH1 to TH2 response by modulating the production of cytokines. A role of the ECS in B-cell differentiation is supported by the finding in CB2 knockout mice that are deficient in a number of B-cell subsets including marginal zone and peritoneal B cells.