The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal

B-1 cells are a distinct lineage of tissue-resident B cells with crucial roles in innate immunity and tissue homeostasis. Mature B-1 cell pools are mostly maintained by self-renewal in their peripheral niches, in a process that is largely uncharacterized. Here, we investigated the role of the transc...

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Main Authors: Seung-Gen Oh, Jeonghyun Noh, Eunkyeong Jang, Jeehee Youn
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1553089/full
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author Seung-Gen Oh
Jeonghyun Noh
Eunkyeong Jang
Jeehee Youn
Jeehee Youn
author_facet Seung-Gen Oh
Jeonghyun Noh
Eunkyeong Jang
Jeehee Youn
Jeehee Youn
author_sort Seung-Gen Oh
collection DOAJ
description B-1 cells are a distinct lineage of tissue-resident B cells with crucial roles in innate immunity and tissue homeostasis. Mature B-1 cell pools are mostly maintained by self-renewal in their peripheral niches, in a process that is largely uncharacterized. Here, we investigated the role of the transcription repressor Bach2 in maintaining the B-1 cell pool. We found that B-1 cell numbers and antibody responses were dramatically reduced in adult mice bearing a B cell-specific Bach2 deletion, although the proportions of B-1 progenitors in early neonatal life were unaffected. Cells taken from the fetal liver or bone marrow of Bach2-deleted mice were defective in reconstituting the B-1 cell pool in the peritonea of Rag2-/- hosts, and peritoneal B-1 cell transplants from adult Bach2-deleted mice failed to sustain their numbers in the host’s peritoneum. The mutant B-1 cells proliferated normally in vivo but were more apoptotic. They also expressed the reduced level of the self-renewal factor Bmi1. These results indicate that Bach2 deficiency does not affect the development of B-1 progenitors in fetal liver and bone marrow but impairs the self-renewal of mature B-1 cells in peripheral tissues, which is caused by increased apoptosis. Thus, this study suggests that a cell-autonomous function of Bach2 is crucial for maintaining a stable population size of B-1 cells in their peripheral niches.
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spelling doaj-art-bc73dcb2780647e9ae2c5a8238e687732025-08-20T02:56:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15530891553089The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewalSeung-Gen Oh0Jeonghyun Noh1Eunkyeong Jang2Jeehee Youn3Jeehee Youn4Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of KoreaDepartment of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of KoreaLaboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, Republic of KoreaDepartment of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of KoreaLaboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, Republic of KoreaB-1 cells are a distinct lineage of tissue-resident B cells with crucial roles in innate immunity and tissue homeostasis. Mature B-1 cell pools are mostly maintained by self-renewal in their peripheral niches, in a process that is largely uncharacterized. Here, we investigated the role of the transcription repressor Bach2 in maintaining the B-1 cell pool. We found that B-1 cell numbers and antibody responses were dramatically reduced in adult mice bearing a B cell-specific Bach2 deletion, although the proportions of B-1 progenitors in early neonatal life were unaffected. Cells taken from the fetal liver or bone marrow of Bach2-deleted mice were defective in reconstituting the B-1 cell pool in the peritonea of Rag2-/- hosts, and peritoneal B-1 cell transplants from adult Bach2-deleted mice failed to sustain their numbers in the host’s peritoneum. The mutant B-1 cells proliferated normally in vivo but were more apoptotic. They also expressed the reduced level of the self-renewal factor Bmi1. These results indicate that Bach2 deficiency does not affect the development of B-1 progenitors in fetal liver and bone marrow but impairs the self-renewal of mature B-1 cells in peripheral tissues, which is caused by increased apoptosis. Thus, this study suggests that a cell-autonomous function of Bach2 is crucial for maintaining a stable population size of B-1 cells in their peripheral niches.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1553089/fullB-1 cellsBACH2self-renewalB-1 cell reconstitutionconditional knockout mouse model
spellingShingle Seung-Gen Oh
Jeonghyun Noh
Eunkyeong Jang
Jeehee Youn
Jeehee Youn
The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal
Frontiers in Immunology
B-1 cells
BACH2
self-renewal
B-1 cell reconstitution
conditional knockout mouse model
title The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal
title_full The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal
title_fullStr The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal
title_full_unstemmed The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal
title_short The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal
title_sort transcription repressor bach2 is required for maintaining the b 1 cell population by regulating self renewal
topic B-1 cells
BACH2
self-renewal
B-1 cell reconstitution
conditional knockout mouse model
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1553089/full
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