Suppression by Δ9-tetrahydrocannabinol of the primary immunoglobulin M response by human peripheral blood B cells is associated with impaired STAT3 activation

This study was undertaken to gain insights into the mechanism for Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-mediated suppression of primary immunoglobulin M (IgM) responses in humans. An in vitro activation model, which employs cell surface-expressed CD40 ligand (CD40L) and recombinant cytokines (interleukin (IL)-2, -6, and -10), was used to differentiate human peripheral blood (HPB) naive B cells into IgM secreting cells. Pretreatment with Delta(9)-THC significantly decreased the number of IgM secreting cells as determined by ELISPOT. The attenuation of IgM secretion by Delta(9)-THC involved, at least in part, the impairment of plasma cell differentiation as evidenced by suppression of immunoglobulin joining chain (IgJ) mRNA expression. The analysis at each of two different stages critically involved in plasma cell differentiation indicates that Delta(9)-THC impaired both the primary activation stage and proliferation of B cells. Interestingly, Delta(9)-THC selectively suppressed the surface expression of CD80, but not other measured B-cell activation markers (CD69, CD86, and ICAM1). Furthermore, pretreatment with Delta(9)-THC was accompanied by a robust decrease of STAT3 phosphorylation, whereas the phosphorylation of the p65 NF kappa B subunit was not affected. Collectively, these data provide new insights into the mechanisms for impaired B cell function by Delta(9)-THC. (c) 2013 Elsevier Ireland Ltd. All rights reserved.