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Sci Rep. 2016 Nov 29;6:37988. doi: 10.1038/srep37988.

Global gene regulation during activation of immunoglobulin class switching in human B cells.

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Molecular Genomics and Genetics Group, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, United Kingdom.


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.

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