IgE production is enhanced by novel signaling intermediates activated by stimulation of a G-protein coupled receptor on a B cell (37.12)

Abstract

Abstract The level of a Th2/IL-4-dependent antibody response is regulated by extrinsic homeostatic signals that stimulate a G-protein coupled receptor, the beta2-adrenergic receptor (β2AR), which is expressed on a B cell. We find that stimulation of the β2AR on a CD40L- and IL-4-activated B cell increases the rate of IgE mRNA transcription and the amount of IgE produced per cell, without affecting class switch recombination. Our data also show that β2AR stimulation increases IgE production in a p38 MAPK−, CD23−, and CD21/CD19-dependent manner above that induced by CD40L/IL-4 alone (J. Immunol., 177:2926). However, the mechanism(s) by which β2AR stimulation on a B cell leads to an increase in p38 MAPK activity remains unknown. Our findings suggest that the β2AR-induced increase in p38 MAPK activity occurs in a PKA-dependent, CREB-independent manner that may involve hematopoietic protein tyrosine phosphatase (HePTP) regulation as determined using gene-deficient and -transgenic mice, enzyme activation assays, co-immunoprecipitation, western blot analysis, and pharmacological inhibitors. We also show that p38 MAPK activation is necessary for a release of CD23 from the cell surface (sCD23), which may be mediated by an increase in ADAM8/10 activity. Thus, the β2AR-induced increase in IgE may depend on a p38 MAPK-induced increase in the level of soluble CD23. Supported by NIH RO1 AI37326.