Cleavage of CD23 by ADAM proteins is regulated by beta-2 adrenergic receptor stimulation on B cells (91.14)

Abstract

Abstract The level of IgE is often associated with the severity of allergic asthma. Beta-2 adrenergic receptor (β2AR) agonists alleviate bronchoconstriction by targeting the β2AR on bronchiolar smooth muscle cells, triggering airway relaxation. The β2AR is also expressed on B lymphocytes. In vitro data from our laboratory showed that β2AR stimulation on a CD40L/IL-4 activated B cell increases the level of IgE produced per cell, without affecting class switch recombination. We also found that surface CD23 expression remained constant, while CD23 mRNA, total CD23 protein, and CD23 cleavage increased. We know that soluble CD23 positively regulates IgE production. Therefore, β2AR stimulation may worsen bronchoconstriction over time, while relieving it in the short term. We hypothesized that the primary sheddase of CD23, ADAM10, was regulated by β2AR stimulation on the activated B cell. However, we found that β2AR stimulation was unable to affect the level of ADAM10 protein or mRNA in an activated B cell as compared to activated cells alone. Our recent data indicated that ADAM8 and ADAM28 might instead be involved in the β2AR-associated shedding of CD23. The differential β2AR-associated ADAM protein cleavage of CD23 may provide a potential molecular target to prevent a β2AR agonist-induced increase in IgE, which may counteract the therapeutic effect to relieve bronchoconstriction. Funded by NIH-AI-37326 and T32-AI55411