The level of IgE produced by a B cell is regulated by norepinephrine in a p38 MAPK- and CD23-dependent manner.

Published

Journal Article

Although the causes of asthma vary, the severity of the disease correlates with the level of IgE produced. In this study we show that mice produced less IgE when they were depleted of the neurotransmitter norepinephrine (NE) before the administration of Ag. The suppression was prevented when a beta2-adrenergic receptor (beta2AR)-selective agonist was administered, suggesting that NE stimulated the beta2AR to regulate the level of an IgE response in vivo. Although the cell targeted by NE to produce this effect in vivo is unknown, we show in vitro that the level of IgE increased on a per cell basis without an effect on class switch recombination when NE stimulated the beta2AR on a B cell directly. The beta2AR-induced increase in IgE depended on p38 MAPK but not protein kinase A activation, was due to an increased rate of mature IgE mRNA transcription, and was lost when beta2AR-deficient B cells were used. Also, CD23 transcription was increased in a p38 MAPK-dependent manner and resulted in an increased level of soluble CD23 (sCD23). The beta2AR-induced increase in sCD23 was associated with IgE up-regulation and possibly interacted with CD21/CD19. Using B cells from respective knockout mice, data showed that the beta2AR-induced increase in IgE depended on B cell expression of CD23, CD21, and CD19. These findings suggest that at least one mechanism by which endogenous B cell activity in vivo is regulated by NE involves stimulation of the beta2AR on the B cell alone to increase the level of IgE produced in a p38 MAPK- and sCD23-dependent manner.

Full Text

Cited Authors

  • Pongratz, G; McAlees, JW; Conrad, DH; Erbe, RS; Haas, KM; Sanders, VM

Published Date

  • September 2006

Published In

Volume / Issue

  • 177 / 5

Start / End Page

  • 2926 - 2938

PubMed ID

  • 16920928

Pubmed Central ID

  • 16920928

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.177.5.2926

Language

  • eng