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

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Title: Global gene regulation during activation of immunoglobulin class switching in human B cells
Authors: Zhang, Y
Fear, D
Willis-Owen, S
Cookson, W
Moffatt, M
Item Type: Journal Article
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.
Issue Date: 29-Nov-2016
Date of Acceptance: 3-Nov-2016
URI: http://hdl.handle.net/10044/1/42297
DOI: https://dx.doi.org/10.1038/srep37988
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 6
Copyright Statement: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Wellcome Trust
National Institute for Health Research
Funder's Grant Number: EP/C509463/1
Publication Status: Published
Article Number: 37988
Appears in Collections:National Heart and Lung Institute