Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE.
J Exp Med
; 214(1): 183-196, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27994069
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Imunoglobulina E
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Linfócitos B
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Switching de Imunoglobulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article