BACH2 in human plasma cell fate decision
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE102460 | GEO | 2017/08/29
SECONDARY ACCESSION(S): PRJNA397793
REPOSITORIES: GEO
Similar Datasets
Project description:To explore events that govern the differentiation of human naïve B cells (NBCs) into memory B cells and plasma cells (PCs), we designed an in vitro 2-step culture model leading non-switched NBC precursors to differentiate into two cell compartments: CD20loCD38hi and CD20+CD38+. Both populations are characterized by distinct cell fates, the former one corresponding to plasmablasts that undergo PC terminal differentiation, with intermingled relationship between cell division and bona fide differentiation two events that are usually viewed as mutually exclusive. Postulating that extracellular cues mediated by distinct receptor-ligand interactions are likely involved in this phenomenon we explored one by one factors used in our model and found that T-cell-produced IL-2 was critical for the PC’s commitment. Interestingly, this IL-2 effect operates independently of proliferation and survival functions and required an ERK signaling. Based on our study we proposed to complete previous scheme of PRDM1/Blimp-1 controlling PC differentiation by adding the T-cell-delivered IL-2 effect, which sustains indirectly the mitogenic-induced Blimp-1 expression by downregulating IRF8 and BACH2 via an ERK signal This study highlight early events that could take place when cognate B and T cells meet and interact before seeding follicle, where crucial inputs may condition final GC B destiny. GEP was performed on the RNA of purified B cells from 3 healthy blood donors, stimulated at Day 0 and with addition or not of IL-2. Four time points were assessed Day 0, Day 0+16h, Day 0+22h and Day 4.
2012-04-08 | E-GEOD-36975 | biostudies-arrayexpress
Project description:To explore events that govern the differentiation of human naïve B cells (NBCs) into memory B cells and plasma cells (PCs), we designed an in vitro 2-step culture model leading non-switched NBC precursors to differentiate into two cell compartments: CD20loCD38hi and CD20+CD38+. Both populations are characterized by distinct cell fates, the former one corresponding to plasmablasts that undergo PC terminal differentiation, with intermingled relationship between cell division and bona fide differentiation two events that are usually viewed as mutually exclusive. Postulating that extracellular cues mediated by distinct receptor-ligand interactions are likely involved in this phenomenon we explored one by one factors used in our model and found that T-cell-produced IL-2 was critical for the PC’s commitment. Interestingly, this IL-2 effect operates independently of proliferation and survival functions and required an ERK signaling. Based on our study we proposed to complete previous scheme of PRDM1/Blimp-1 controlling PC differentiation by adding the T-cell-delivered IL-2 effect, which sustains indirectly the mitogenic-induced Blimp-1 expression by downregulating IRF8 and BACH2 via an ERK signal This study highlight early events that could take place when cognate B and T cells meet and interact before seeding follicle, where crucial inputs may condition final GC B destiny.
2012-04-09 | GSE36975 | GEO
Project description:Differentiation and homeostasis of Foxp3 + regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis by directly repressed CD25 (IL-2Rα). Thus, Bach2 balances IL-2R signaling to orchestrate development and homeostasis of various Treg subsets.
2021-05-11 | GSE164937 | GEO
Project description:Bach2 codes for a transcriptional regulator exerting major influences on T cell mediated immune regulation. Effector CTLs derived from in vitro activation of murine CD8+ T cells showed increased proliferative and cytolytic capacity in the absence of BACH2. Before activation, BACH2-deficient CD8+ T cells had a higher abundance of memory and reduced abundance of naïve cells compared to wild-type. CTLs derived from central memory T cells were more potently cytotoxic than those derived from naïve T cells, but even within separated subsets, BACH2-deficiency conferred a cytotoxic advantage. Immunofluorescence and electron microscopy revealed larger granules in BACH2-deficient compared to wild-type CTLs, and proteomic analysis showed an increase in granule content, including perforin and granzymes. Thus, the enhanced cytotoxicity observed in effector CTLs lacking BACH2 arises not only from differences in their initial differentiation state but also inherent production of enlarged cytolytic granules. These results demonstrate how a single gene deletion can produce a CTL super-killer.
2022-09-02 | PXD036457 | Pride
Project description:Long-term humoral immunity is partly maintained by memory B cells (MBCs). MBCs can be recalled to produce antibody-producing plasma cells (PCs) or form secondary germinal centers (GCs). The former process underlies markedly increased antigen-specific antibodies seen in the secondary response, while the latter process allows continuous somatic hypermutation and affinity maturation. MBC re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza and HIV. However, how MBC recall is transcriptionally or epigenetically programmed to produce secondary PCs or GCs is not yet understood. Here we show that BACH2, a transcription factor required for GC formation and maintenance1,2, decreases across post-activation stages of B cells, from the naïve state to GC, memory, and the terminal PC state. In contrast, BLIMP-1, a transcription factor that promotes PC formation3,4 and is antagonistic to BACH2 (ref. 5), increases as B cells traverse the same course. The relative strength between BLIMP-1 and BACH2 progressively increases in favor of BLIMP-1 in GCs and MBCs through the primary response. MBCs of the isotype or subset identity that preferentially give rise to secondary GCs exhibit comparatively higher BACH2 but lower BLIMP-1 expression than those predisposed for PC formation. Using a tetracycline-controlled circuit implanted in MBCs, we show that skewing the BLIMP-1-BACH2 balance in favor of BACH2 markedly increases GC formation by otherwise PC-predisposed MBCs, whereas skewing the balance in favor of BLIMP-1 drives PC formation by GC-prone MBCs, indicating that the potential for GC re-participation or PC development rests in the relative strength of BLIMP-1 over BACH2 within individual MBCs. Underneath this relative BLIMP-1-over-BACH2 strength in naïve B cells, GCs, MBCs and PCs, we observe progressively increased accessibilities to chromatin loci that are specifically opened in PCs, particularly those that contain ISRE elements and are controlled by IRF-4. IRF-4 is universally upregulated in B cells when stimulated through the BCR, the CD40 receptor, or by innate stimuli. By analyzing time-stamped GC B cells, we demonstrate a progressive increase in chromatin accessibilities at PC-specific, IRF-4-controlled gene loci over time. Our results support a model of progressive IRF-4 imprinting in which the cumulative stimulation history of B cells is epigenetically recorded in an IRF-4-dependent manner, determines the relative strength between BLIMP-1 and BACH2 in individual MBCs, and thereby dictates their individual probabilities to develop into GCs or PCs upon re-stimulation.
2024-06-04 | GSE246797 | GEO
Project description:Long-term humoral immunity is partly maintained by memory B cells (MBCs). MBCs can be recalled to produce antibody-producing plasma cells (PCs) or form secondary germinal centers (GCs). The former process underlies markedly increased antigen-specific antibodies seen in the secondary response, while the latter process allows continuous somatic hypermutation and affinity maturation. MBC re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza and HIV. However, how MBC recall is transcriptionally or epigenetically programmed to produce secondary PCs or GCs is not yet understood. Here we show that BACH2, a transcription factor required for GC formation and maintenance1,2, decreases across post-activation stages of B cells, from the naïve state to GC, memory, and the terminal PC state. In contrast, BLIMP-1, a transcription factor that promotes PC formation3,4 and is antagonistic to BACH2 (ref. 5), increases as B cells traverse the same course. The relative strength between BLIMP-1 and BACH2 progressively increases in favor of BLIMP-1 in GCs and MBCs through the primary response. MBCs of the isotype or subset identity that preferentially give rise to secondary GCs exhibit comparatively higher BACH2 but lower BLIMP-1 expression than those predisposed for PC formation. Using a tetracycline-controlled circuit implanted in MBCs, we show that skewing the BLIMP-1-BACH2 balance in favor of BACH2 markedly increases GC formation by otherwise PC-predisposed MBCs, whereas skewing the balance in favor of BLIMP-1 drives PC formation by GC-prone MBCs, indicating that the potential for GC re-participation or PC development rests in the relative strength of BLIMP-1 over BACH2 within individual MBCs. Underneath this relative BLIMP-1-over-BACH2 strength in naïve B cells, GCs, MBCs and PCs, we observe progressively increased accessibilities to chromatin loci that are specifically opened in PCs, particularly those that contain ISRE elements and are controlled by IRF-4. IRF-4 is universally upregulated in B cells when stimulated through the BCR, the CD40 receptor, or by innate stimuli. By analyzing time-stamped GC B cells, we demonstrate a progressive increase in chromatin accessibilities at PC-specific, IRF-4-controlled gene loci over time. Our results support a model of progressive IRF-4 imprinting in which the cumulative stimulation history of B cells is epigenetically recorded in an IRF-4-dependent manner, determines the relative strength between BLIMP-1 and BACH2 in individual MBCs, and thereby dictates their individual probabilities to develop into GCs or PCs upon re-stimulation.
2024-06-04 | GSE246800 | GEO
Project description:Long-term humoral immunity is partly maintained by memory B cells (MBCs). MBCs can be recalled to produce antibody-producing plasma cells (PCs) or form secondary germinal centers (GCs). The former process underlies markedly increased antigen-specific antibodies seen in the secondary response, while the latter process allows continuous somatic hypermutation and affinity maturation. MBC re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza and HIV. However, how MBC recall is transcriptionally or epigenetically programmed to produce secondary PCs or GCs is not yet understood. Here we show that BACH2, a transcription factor required for GC formation and maintenance1,2, decreases across post-activation stages of B cells, from the naïve state to GC, memory, and the terminal PC state. In contrast, BLIMP-1, a transcription factor that promotes PC formation3,4 and is antagonistic to BACH2 (ref. 5), increases as B cells traverse the same course. The relative strength between BLIMP-1 and BACH2 progressively increases in favor of BLIMP-1 in GCs and MBCs through the primary response. MBCs of the isotype or subset identity that preferentially give rise to secondary GCs exhibit comparatively higher BACH2 but lower BLIMP-1 expression than those predisposed for PC formation. Using a tetracycline-controlled circuit implanted in MBCs, we show that skewing the BLIMP-1-BACH2 balance in favor of BACH2 markedly increases GC formation by otherwise PC-predisposed MBCs, whereas skewing the balance in favor of BLIMP-1 drives PC formation by GC-prone MBCs, indicating that the potential for GC re-participation or PC development rests in the relative strength of BLIMP-1 over BACH2 within individual MBCs. Underneath this relative BLIMP-1-over-BACH2 strength in naïve B cells, GCs, MBCs and PCs, we observe progressively increased accessibilities to chromatin loci that are specifically opened in PCs, particularly those that contain ISRE elements and are controlled by IRF-4. IRF-4 is universally upregulated in B cells when stimulated through the BCR, the CD40 receptor, or by innate stimuli. By analyzing time-stamped GC B cells, we demonstrate a progressive increase in chromatin accessibilities at PC-specific, IRF-4-controlled gene loci over time. Our results support a model of progressive IRF-4 imprinting in which the cumulative stimulation history of B cells is epigenetically recorded in an IRF-4-dependent manner, determines the relative strength between BLIMP-1 and BACH2 in individual MBCs, and thereby dictates their individual probabilities to develop into GCs or PCs upon re-stimulation.
2024-06-04 | GSE246799 | GEO
Project description:Long-term humoral immunity is partly maintained by memory B cells (MBCs). MBCs can be recalled to produce antibody-producing plasma cells (PCs) or form secondary germinal centers (GCs). The former process underlies markedly increased antigen-specific antibodies seen in the secondary response, while the latter process allows continuous somatic hypermutation and affinity maturation. MBC re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza and HIV. However, how MBC recall is transcriptionally or epigenetically programmed to produce secondary PCs or GCs is not yet understood. Here we show that BACH2, a transcription factor required for GC formation and maintenance1,2, decreases across post-activation stages of B cells, from the NAIVE state to GC, memory, and the terminal PC state. In contrast, BLIMP-1, a transcription factor that promotes PC formation3,4 and is antagonistic to BACH2 (ref. 5), increases as B cells traverse the same course. The relative strength between BLIMP-1 and BACH2 progressively increases in favor of BLIMP-1 in GCs and MBCs through the primary response. MBCs of the isotype or subset identity that preferentially give rise to secondary GCs exhibit comparatively higher BACH2 but lower BLIMP-1 expression than those predisposed for PC formation. Using a tetracycline-controlled circuit implanted in MBCs, we show that skewing the BLIMP-1-BACH2 balance in favor of BACH2 markedly increases GC formation by otherwise PC-predisposed MBCs, whereas skewing the balance in favor of BLIMP-1 drives PC formation by GC-prone MBCs, indicating that the potential for GC re-participation or PC development rests in the relative strength of BLIMP-1 over BACH2 within individual MBCs. Underneath this relative BLIMP-1-over-BACH2 strength in NAIVE B cells, GCs, MBCs and PCs, we observe progressively increased accessibilities to chromatin loci that are specifically opened in PCs, particularly those that contain ISRE elements and are controlled by IRF-4. IRF-4 is universally upregulated in B cells when stimulated through the BCR, the CD40 receptor, or by innate stimuli. By analyzing time-stamped GC B cells, we demonstrate a progressive increase in chromatin accessibilities at PC-specific, IRF-4-controlled gene loci over time. Our results support a model of progressive IRF-4 imprinting in which the cumulative stimulation history of B cells is epigenetically recorded in an IRF-4-dependent manner, determines the relative strength between BLIMP-1 and BACH2 in individual MBCs, and thereby dictates their individual probabilities to develop into GCs or PCs upon re-stimulation.
2024-06-04 | GSE267568 | GEO
Project description:Long-term humoral immunity is partly maintained by memory B cells (MBCs). MBCs can be recalled to produce antibody-producing plasma cells (PCs) or form secondary germinal centers (GCs). The former process underlies markedly increased antigen-specific antibodies seen in the secondary response, while the latter process allows continuous somatic hypermutation and affinity maturation. MBC re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza and HIV. However, how MBC recall is transcriptionally or epigenetically programmed to produce secondary PCs or GCs is not yet understood. Here we show that BACH2, a transcription factor required for GC formation and maintenance1,2, decreases across post-activation stages of B cells, from the naïve state to GC, memory, and the terminal PC state. In contrast, BLIMP-1, a transcription factor that promotes PC formation3,4 and is antagonistic to BACH2 (ref. 5), increases as B cells traverse the same course. The relative strength between BLIMP-1 and BACH2 progressively increases in favor of BLIMP-1 in GCs and MBCs through the primary response. MBCs of the isotype or subset identity that preferentially give rise to secondary GCs exhibit comparatively higher BACH2 but lower BLIMP-1 expression than those predisposed for PC formation. Using a tetracycline-controlled circuit implanted in MBCs, we show that skewing the BLIMP-1-BACH2 balance in favor of BACH2 markedly increases GC formation by otherwise PC-predisposed MBCs, whereas skewing the balance in favor of BLIMP-1 drives PC formation by GC-prone MBCs, indicating that the potential for GC re-participation or PC development rests in the relative strength of BLIMP-1 over BACH2 within individual MBCs. Underneath this relative BLIMP-1-over-BACH2 strength in naïve B cells, GCs, MBCs and PCs, we observe progressively increased accessibilities to chromatin loci that are specifically opened in PCs, particularly those that contain ISRE elements and are controlled by IRF-4. IRF-4 is universally upregulated in B cells when stimulated through the BCR, the CD40 receptor, or by innate stimuli. By analyzing time-stamped GC B cells, we demonstrate a progressive increase in chromatin accessibilities at PC-specific, IRF-4-controlled gene loci over time. Our results support a model of progressive IRF-4 imprinting in which the cumulative stimulation history of B cells is epigenetically recorded in an IRF-4-dependent manner, determines the relative strength between BLIMP-1 and BACH2 in individual MBCs, and thereby dictates their individual probabilities to develop into GCs or PCs upon re-stimulation.
2024-06-04 | GSE267566 | GEO
Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which self renew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineage commitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis. This SuperSeries is composed of the SubSeries listed below.
2020-05-12 | GSE128176 | GEO