科研之友
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摘要
Soluble CD23 plays a role in the positive regulation of an IgE response. Engagement of the beta(2) adrenergic receptor (beta(2)AR) on a B cell is known to enhance the level of both soluble CD23 and IgE, although the mechanism by which this occurs is not completely understood. In this study, we report that, in comparison with a CD40 ligand/IL-4-primed murine B cell alone, beta(2)AR engagement on a primed B cell increased gene expression of a disintegrin and metalloproteinase (ADAM) 10, which is the primary sheddase of CD23, as well as protein expression of both CD23 and ADAM10, in a protein kinase A-and p38 MAPK-dependent manner, and promoted the localization of these proteins to exosomes as early as 2 d after priming, as determined by both Western blot and flow cytometry and confirmed by electron microscopy. In comparison with isolated exosomes released from primed B cells alone, the transfer of exosomes released from beta(2)AR agonist-exposed primed B cells to cultures of recipient primed B cells resulted in an increase in the level of IgE produced per cell, without affecting the number of cells producing IgE, as determined by ELISPOT. These effects still occurred when a beta(2)AR antagonist was added along with the transfer to block residual agonist, and they failed to occur when exosomes were isolated from beta(2)AR-deficient B cells. These findings suggest that the mechanism responsible for mediating the beta(2)AR-induced increase in IgE involves a shuttling of the beta(2)AR-induced increase in CD23 and ADAM10 proteins to exosomes that subsequently mediate an increase in IgE.
- 出版日期2013-12-1
