title: FCER2 (CD23) asthma-related single nucleotide polymorphisms yields increased IgE binding and Egr-1 expression in human B cells.
abstract: CD23 is the low-affinity Fc receptor for IgE. When expressed on B cells, CD23 appears to play a role in regulation of IgE synthesis. Polymorphisms within FCER2, the gene encoding CD23, have been associated with atopy, increased risk of exacerbations in patients with asthma, and high serum IgE levels. A single-nucleotide polymorphism (rs2228137) present in exon 4 of FCER2 encodes a nonsynonymous amino acid change (R62W) and is the subject of the present analysis. Human B cell stable transfectants were established to characterize the functional relevance of the R62W SNP. We demonstrate that CD23b-R62W-expressing human B cells bind IgE with greater affinity than wild-type cells and display differences in kinetics of CD23-mediated ERK1/2 activation that may be responsible for the increased levels of Egr-1 mRNA observed after stimulation through CD23. Finally, the R62W SNP seems to alter the tertiary or quaternary structure of CD23 because in the absence of N-glycosylation the CD23b-R62W-expressing cells appear to be less sensitive to endogenous proteases. These observations may have implications in mechanisms responsible for the atopic phenotypes observed in patients with asthma who possess this genotype.
authors.affiliation: Department of Pediatrics, Division of Immunology Research, Children's Mercy Hospitals & Clinics, Kansas City, Missouri.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Chan
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Gigliotti
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Aubin
authors.forename: Lanny J
authors.initials: LJ
authors.lastname: Rosenwasser
mesh_terms: D001249:Asthma / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051766:Early Growth Response Protein 1; C546930:FCER2 protein, human; D037181:Lectins, C-Type; D017455:Receptors, IgE; D007073:Immunoglobulin E