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The Level of IgE Produced by a B Cell Is Regulated by Norepinephrine in a p38 MAPK- and CD23-Dependent Manner¹

Georg Pongratz^*, Jaclyn W. McAlees^*, Daniel H. Conrad, Robert S. Erbe^*, Karen M. Haas and Virginia M. Sanders^2,*

^* Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298; and Department of Immunology, Duke University Medical Center, Durham, NC 27710

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 ₂-adrenergic receptor (₂AR)-selective agonist was administered, suggesting that NE stimulated the ₂AR 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 ₂AR on a B cell directly. The ₂AR-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 ₂AR-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 ₂AR-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 ₂AR-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 ₂AR on the B cell alone to increase the level of IgE produced in a p38 MAPK- and sCD23-dependent manner.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grants AI37326 and A147420 (to V.M.S.) and Deutsche Forschungsgemeinschaft Grant PO 801/1-1 (to G.P.).

² Address correspondence and reprint requests to Dr. Virginia Sanders, Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, 2194 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210. E-mail address: sanders.302{at}osu.edu

³ Abbreviations used in this paper: BAL, bronchoalveolar lavage; AR, adrenergic receptor; ATF-2, activating transcription factor 2; BALT, bronchus-associated lymphatic tissue; CSR, class switch recombination; GC, germinal center; i.t., intratracheal(ly); mCD23, membrane-bound CD23; NE, norepinephrine; sCD23, soluble CD23; 6-OHDA, 6-hydroxydopamine; PKA, protein kinase.

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