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Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE
Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206502/ https://www.ncbi.nlm.nih.gov/pubmed/27994069 http://dx.doi.org/10.1084/jem.20161056 |
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author | Wu, Yee Ling Stubbington, Michael J.T. Daly, Maria Teichmann, Sarah A. Rada, Cristina |
author_facet | Wu, Yee Ling Stubbington, Michael J.T. Daly, Maria Teichmann, Sarah A. Rada, Cristina |
author_sort | Wu, Yee Ling |
collection | PubMed |
description | Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4–induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma. |
format | Online Article Text |
id | pubmed-5206502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52065022017-07-01 Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE Wu, Yee Ling Stubbington, Michael J.T. Daly, Maria Teichmann, Sarah A. Rada, Cristina J Exp Med Research Articles Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4–induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma. The Rockefeller University Press 2017-01 /pmc/articles/PMC5206502/ /pubmed/27994069 http://dx.doi.org/10.1084/jem.20161056 Text en © 2017 Wu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Wu, Yee Ling Stubbington, Michael J.T. Daly, Maria Teichmann, Sarah A. Rada, Cristina Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE |
title | Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE |
title_full | Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE |
title_fullStr | Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE |
title_full_unstemmed | Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE |
title_short | Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE |
title_sort | intrinsic transcriptional heterogeneity in b cells controls early class switching to ige |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206502/ https://www.ncbi.nlm.nih.gov/pubmed/27994069 http://dx.doi.org/10.1084/jem.20161056 |
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