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The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development
Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, by single-cell RNA-seq analysis, we identified a population of germinal center (GC) B cells in the process of differentiating into MBCs. U...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442689/ https://www.ncbi.nlm.nih.gov/pubmed/32601467 http://dx.doi.org/10.1038/s41590-020-0713-6 |
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author | Laidlaw, Brian J. Duan, Lihui Xu, Ying Vazquez, Sara E. Cyster, Jason G. |
author_facet | Laidlaw, Brian J. Duan, Lihui Xu, Ying Vazquez, Sara E. Cyster, Jason G. |
author_sort | Laidlaw, Brian J. |
collection | PubMed |
description | Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, by single-cell RNA-seq analysis, we identified a population of germinal center (GC) B cells in the process of differentiating into MBCs. Using an inducible Crispr/Cas9 screening approach we identified the hematopoietically expressed homeobox gene Hhex as a transcription factor regulating MBC differentiation. The co-repressor Tle3 was also identified in the screen and was found to interact with Hhex to promote MBC development. Bcl-6 directly repressed Hhex in GC B cells. Reciprocally, Hhex-deficient MBCs exhibited derepressed Bcl6 and reduced expression of Bcl-6-repressed Bcl2. Overexpression of Bcl-2 was able to rescue MBC differentiation in Hhex-deficient cells. We also identified Ski as an Hhex-induced transcription factor involved in MBC differentiation. These findings establish an important role for Hhex-Tle3 in regulating the transcriptional circuitry governing MBC differentiation. |
format | Online Article Text |
id | pubmed-7442689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-74426892020-12-29 The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development Laidlaw, Brian J. Duan, Lihui Xu, Ying Vazquez, Sara E. Cyster, Jason G. Nat Immunol Article Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, by single-cell RNA-seq analysis, we identified a population of germinal center (GC) B cells in the process of differentiating into MBCs. Using an inducible Crispr/Cas9 screening approach we identified the hematopoietically expressed homeobox gene Hhex as a transcription factor regulating MBC differentiation. The co-repressor Tle3 was also identified in the screen and was found to interact with Hhex to promote MBC development. Bcl-6 directly repressed Hhex in GC B cells. Reciprocally, Hhex-deficient MBCs exhibited derepressed Bcl6 and reduced expression of Bcl-6-repressed Bcl2. Overexpression of Bcl-2 was able to rescue MBC differentiation in Hhex-deficient cells. We also identified Ski as an Hhex-induced transcription factor involved in MBC differentiation. These findings establish an important role for Hhex-Tle3 in regulating the transcriptional circuitry governing MBC differentiation. 2020-06-29 2020-09 /pmc/articles/PMC7442689/ /pubmed/32601467 http://dx.doi.org/10.1038/s41590-020-0713-6 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Laidlaw, Brian J. Duan, Lihui Xu, Ying Vazquez, Sara E. Cyster, Jason G. The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development |
title | The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development |
title_full | The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development |
title_fullStr | The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development |
title_full_unstemmed | The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development |
title_short | The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development |
title_sort | transcription factor hhex cooperates with the corepressor tle3 to promote memory b cell development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442689/ https://www.ncbi.nlm.nih.gov/pubmed/32601467 http://dx.doi.org/10.1038/s41590-020-0713-6 |
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