期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 1, 页码 183-196出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161056
关键词
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资金
- Medical Research Council [MC_U105178806]
- Ruth L. Kirschstein National Research Service Award from the National Institute of Allergy and Infectious Diseases, National Institutes of Health [F32AI091311]
- European Research Council ThSWI TCH grant [260507]
- Medical Research Council [MC_U105178805] Funding Source: researchfish
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [F32AI091311] Funding Source: NIH RePORTER
- MRC [MC_U105178805, MC_U105178806] Funding Source: UKRI
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 I epsilon and I gamma 1 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 I epsilon but not I gamma 1 and demonstrate that early I epsilon transcription leads to switching to IgE and occurs at lower activation levels than I gamma 1. Our results reveal how probabilistic transcription with a lower activation threshold for I epsilon directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma.
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