Stimulation of the B cell receptor, CD86 (B7-2), and the β₂-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per B cell

Our findings using B cells from either wild-type, CD86-deficient, or β₂-adrenergic receptor (β₂AR)-deficient mice suggest three mechanisms by which the level of IgG1 and IgE production can be increased on a per cell basis. Trinitrophenyl-specific B cells enriched from unimmunized mouse spleens were pre-exposed to Ag and/or the β₂AR ligand terbutaline for 24 h before being activated by either a β₂AR-negative Th2 cell clone or CD40 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)-dependent up-regulation of CD86 expression that, when CD86 is stimulated, increases the amount of IgG1 and IgE produced in comparison to unstimulated cells. The second mechanism involves a BCR-and β₂AR-dependent up-regulation of CD86 to a level higher than that induced by stimulation of either receptor alone that, when CD86 is stimulated, further increases the amount of IgG1 and IgE produced. The third mechanism is BCR-independent and involves a β₂AR- dependent increase in the ability of a B cell to respond to IL-4. Flow cytometric and limiting dilution analyses suggest that the increase in IgG1 and IgE occurs independently from the isotype switching event. These findings suggest that the BCR, the β₂AR, and CD86 are involved in regulating IL-4- dependent IgG1 and IgE production.