title: Global gene regulation during activation of immunoglobulin class switching in human B cells.
abstract: Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed. CCL22 and CCL17 were dramatically induced but followed a temporal trajectory distinct from classical mediators of isotype switching. AICDA, NFIL3, IRF4, XBP1 and BATF3 shared a profile with several genes involved in innate immunity, but with no recognised role in CSR. A transcription factor BHLHE40 was identified at the core of this profile. B-cell activation was also accompanied by variation in exon retention affecting >200 genes including CCL17. The data indicate a circadian component and central roles for the Th2 chemokines CCL22 and CCL17 in the activation of CSR.
authors.affiliation: Molecular Genomics and Genetics Group, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Youming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Fear
authors.affiliation: Molecular Genomics and Genetics Group, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Saffron A G
authors.initials: SA
authors.lastname: Willis-Owen
authors.affiliation: Molecular Genomics and Genetics Group, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: William O
authors.initials: WO
authors.lastname: Cookson
authors.affiliation: Molecular Genomics and Genetics Group, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology
chemical_list: D007132:Immunoglobulin Isotypes