Env, Env-APRIL, Env-BAFF, and Env-CD40L induce AID expression and Ig secretion in human B cells. (A) AID mRNA levels in naïve human B cells stimulated with Env, Env-fusion proteins, or control stimuli were measured by real-time PCR. Negative-control B cells did not receive any stimulus (no IL-4 or IL-10). Positive-control cells received CpG-B in addition to the stimulation cocktail. Similar results were obtained with naïve B cells from three different donors. (B) IgM (left panel), IgG (middle panel), and IgA (right panel) levels in the supernatant of human B cells mock stimulated or stimulated with Env or the respective fusion proteins supplemented with a maturation cocktail were measured by ELISA after 14 days. Similar results were obtained with B cells from three different donors. *, **, and *** indicate P < 0.05, P < 0.01, and P < 0.001, respectively, as determined by a one-tailed Student's t test.