Liver X receptors control IgE expression in B cells.
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.
Heine
Guido
G
Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany.
Dahten
Anja
A
Hilt
Kerstin
K
Ernst
Dennis
D
Milovanovic
Milena
M
Hartmann
Björn
B
Worm
Margitta
M
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
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