Cannabinoid Receptor 2 (CB2) Mediates Immunoglobulin Class Switching from IgM to IgE in Cultures of Murine-Purified B Lymphocytes

摘要

Marijuana cannabinoid treatment increases Th2 activity, and previous reports showed that B cells express the highest level of CB2 mRNA relative to other immune cells, suggesting that cannabinoids play a critical role in B cell activation and maturation. We previously reported evidence of Th2 biasing and class switching in cannabinoid-treated and antigen-challenged mice. We now explore the possibility that cannabinoids directly influence B cell antibody class switching. Mouse splenic B cells were purified by negative selection and cultured with IL4 and anti-CD40 in the presence or absence of the nonselective cannabinoid agonist, CP55940, or the CB1 selective cannabinoid agonist, methanandamide, and analyzed at different days by flow cytometry for surface expression of either IgM or IgE. Cells treated with CP55940 showed an increase in expression of IgE by day 5 in culture; methanandamide had no effect. CP55940 also induced an increase in secreted IgE in culture supernatants as analyzed by ELISA. In addition, CB2 receptors were increased on B cells after stimulation with IL-4 and anti-CD40, and the class switching effect of CP55940 was attenuated by the CB2 antagonist, SR144528. These results suggest that cannabinoids bias toward Th2-type immunity by directly inducing B cell class switching from IgM to IgE through a mechanism involving CB2 receptors.