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Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany
B lymphocytes play a fundamental role in the development of IgE-dependent allergic immune reactions. Upon appropriate activation, IgE class switch recombination is initiated in B cells, followed by terminal differentiation to IgE-secreting plasmablasts. This process is controlled by different nuclear receptors, including receptors for vitamin D, retinoids, and peroxisome proliferator-activated receptor-
ligands. In this study, we show constitutive expression of the nuclear liver X receptor (LXR)
and LXRβ in peripheral human B cells. Activation of LXRs reduced secreted IgE (–68% ± 11) in CD40 and IL-4 activated B cells. The production of other isotypes, including IgG, IgM, IgA and B cell homeostatic parameters were not significantly altered by LXR activation. We identified inhibitory action of LXR activation on IgE production involving reduced phosphorylation of JNK and increased membrane CD23 expression (38% ± 11). The biological significance of our findings was validated by showing that systemic treatment of type I-sensitized BALB/c mice with LXR ligands reduced the serum concentrations of Ag-specific IgE in a dose-dependent manner (maximum, –52% ± 14). Thus, our data indicates that LXRs are involved in the control of IgE secretion by differentiating B cells.
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 is supported by the German Research Foundation (SFB650-TP5) and a grant of Charité Universitätsmedizin Berlin. G.H., A.D., and M.W. designed the experiments and largely wrote the manuscript, G.H., A.D., K.H., M.M., D.E., and B.H. performed and analyzed significant experimental procedures. All authors checked the final version of the manuscript.
2 G.H. and A.D. contributed equally to this work.
3 Address correspondence and reprint requests to Prof. Dr. Margitta Worm, Allergie-Centrum-Charité, Campus Charité Mitte, Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. E-mail address: margitta.worm{at}charite.de
4 Abbreviations used in this paper in this manuscript: LXR, liver X receptor; AID, activation-induced cytidine deaminase; 
GLT, -germline transcription; kgbw, kilogram body weight; sCD23, soluble CD23.
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