title: Liver X receptors control IgE expression in B cells.
abstract: 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-gamma ligands. In this study, we show constitutive expression of the nuclear liver X receptor (LXR)alpha and LXRbeta 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.
authors.affiliation: Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Heine
authors.forename: Anja
authors.initials: A
authors.lastname: Dahten
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hilt
authors.forename: Dennis
authors.initials: D
authors.lastname: Ernst
authors.forename: Milena
authors.initials: M
authors.lastname: Milovanovic
authors.forename: Björn
authors.initials: B
authors.lastname: Hartmann
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000378:metabolism; D019169:Jurkat Cells; D008024:Ligands; D000071518:Liver X Receptors; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D057093:Orphan Nuclear Receptors; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D020033:Protein Isoforms / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013449:Sulfonamides / Q000008:administration & dosage; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D018926:Anti-Allergic Agents; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D007073:Immunoglobulin E; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010047:Ovalbumin; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides