Stimulation of the B cell receptor, CD86 (B7-2), and the beta(2)-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per Bcell

Our findings using B cells from either wild-type, CD86-deficient, or beta(2 )-adrenergic receptor (beta(2)AR)-deficient mice suggest three mechanisms b y which the level of IgG1 and IgE production can be increased on a per cell basis. Trinitrophenyl-specific B cells enriched from unimmunized mouse spl eens were pre-exposed to Ag and/or the beta(2)AR ligand terbutaline for 24 h before being activated by either a beta(2)AR-negative Th2 cell clone or C D40 ligand/Sf9 cells and IL-4 in the presence or absence of an anti-CD86 Ab , Data suggest that the first mechanism involves a B cell receptor (BCR)-de pendent up-regulation of CD86 expression that, when CD86 is stimulated, inc reases the amount of IgG1 and IgE produced in comparison to unstimulated ce lls. The second mechanism involves a BCR- and beta(2)AR-dependent up-regula tion of CD86 to a level higher than that induced by stimulation of either r eceptor alone that, when CD86 is stimulated, further increases the amount o f IgG1 and IgE produced. The third mechanism is BCR-independent and involve s a beta(2)AR-dependent increase in the ability of a B cell to respond to I L-4, Flow cytometric and limiting dilution analyses suggest that the increa se in IgG1 and IgE occurs independently from the isotype switching event, T hese findings suggest that the BCR, the beta(2)AR, and CD86 are involved in regulating IL-4-dependent IgG1 and IgE production.