Cleavage of CD23 by ADAM proteins is regulated by beta-2 adrenergic receptor engagement on primed B cells (55.11)

Abstract

Abstract Allergic asthma severity may be associated with IgE levels. We have shown that beta-2 adrenergic receptor (β2AR) engagement on CD40L/IL-4-primed B cells increases the level of IgE produced per cell, without affecting class switch recombination. β2AR agonists alleviate bronchoconstriction by targeting the β2AR expressed on bronchiolar smooth muscle cells to trigger airway relaxation, but these drugs also target the β2AR on primed B cells, potentially producing an IgE effect that may be counterproductive to the drugs intended use. We reported that surface CD23 expression remained constant on primed B cells exposed to a β2AR agonist, while CD23 mRNA, total CD23 protein, and soluble CD23 (sCD23) increased. Thus, if sCD23 positively regulates IgE production, an increase due to β2AR engagement may worsen bronchoconstriction, albeit relieving it in the short term. We hypothesized that the primary sheddase of CD23, ADAM10, is regulated by β2AR engagement on a primed B cell. Although we found that β2AR engagement was unable to affect the level of ADAM10 protein or mRNA produced compared to primed cells alone, our recent data indicated that the β2AR-induced increase in CD23 shedding may be mediated by increased localization of mature ADAM10 with CD23. Thus, ADAM10 may be a molecular target that can be blocked during β2AR drug therapy to prevent increased sCD23 and IgE, which may counteract the therapeutic bronchorelaxation.