A Role for the Transcription Factor Arid3a in Mouse B2 Lymphocyte Expansion and Peritoneal B1a Generation

Habir, Katrin; Aeinehband, Shahin; Wermeling, Fredrik; Malin, Stephen

doi:10.3389/fimmu.2017.01387

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…In adult mice, the absolute number of B cells in spleen and PerC was unchanged by Arid3a-deficiency ( Figures 3E,F ), and there was no change in the representation of the FO B and MZ B cell populations in the spleen ( Figure 3E ). In contrast, CD5 + B1a cells were completely absent from the PerC of adult Arid3a KO mice ( Figures 3E,F ) as previously found ( 34 ), including those expressing the B1a restricted V H 11 + anti-PtC (phosphatidylcholine) BCR normally found in WT mice ( Figure 3E , right). Distinct from CD5 + CD11b + B1a cell loss, CD5 − CD11b + B1b cells were present in the PerC by Arid3a-deficiency ( Figure 3E ), consistent with the Btk-independence of B1b cell development ( 35 ).…”

Section: Resultssupporting

confidence: 83%

Crucial Role of Increased Arid3a at the Pre-B and Immature B Cell Stages for B1a Cell Generation

Hayakawa

Shinton

et al. 2019

Front. Immunol.

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The Lin28b+Let7− axis in fetal/neonatal development plays a role in promoting CD5+ B1a cell generation as a B-1 B cell developmental outcome. Here we identify the Let7 target, Arid3a, as a crucial molecular effector of the B-1 cell developmental program. Arid3a expression is increased at pro-B cell stage and markedly increased at pre-B and immature B cell stages in the fetal/neonatal liver B-1 development relative to that in the Lin28b−Let7+ adult bone marrow (BM) B-2 cell development. Analysis of B-lineage restricted Lin28b transgenic (Tg) mice, Arid3a knockout and Arid3a Tg mice, confirmed that increased Arid3a allows B cell generation without requiring surrogate light chain (SLC) associated pre-BCR stage, and prevents MHC class II cell expression at the pre-B and newly generated immature B cell stages, distinct from pre-BCR dependent B development with MHC class II in adult BM. Moreover, Arid3a plays a crucial role in supporting B1a cell generation. The increased Arid3a leads higher Myc and Bhlhe41, and lower Siglec-G and CD72 at the pre-B and immature B cell stages than normal adult BM, to allow BCR signaling induced B1a cell generation. Arid3a-deficiency selectively blocks the development of B1a cells, while having no detectable effect on CD5− B1b, MZ B, and FO B cell generation resembling B-2 development outcome. Conversely, enforced expression of Arid3a by transgene is sufficient to promote the development of B1a cells from adult BM. Under the environment change between birth to adult, altered BCR repertoire in increased B1a cells occurred generated from adult BM. However, crossed with B1a-restricted VH/D/J IgH knock-in mice allowed to confirm that SLC-unassociated B1a cell increase and CLL/lymphoma generation can occur in aged from Arid3a increased adult BM. These results confirmed that in fetal/neonatal normal mice, increased Arid3a at the pre-B cell and immature B cell stages is crucial for generating B1a cells together with the environment for self-ligand reactive BCR selection, B1a cell maintenance, and potential for development of CLL/Lymphoma in aged mice.

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Section: Resultssupporting

confidence: 83%

Crucial Role of Increased Arid3a at the Pre-B and Immature B Cell Stages for B1a Cell Generation

Hayakawa

Shinton

et al. 2019

Front. Immunol.

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“…Indeed, ectopic expression of Arid3a in adult pro-B cells enhances B-1a cell generation, while RNAi-mediated knockdown of its expression in FL pro-B cells interferes with B-1a cell differentiation [59]. Consistent with these findings, conditional inactivation of Arid3a results in a severe decrease of peritoneal B-1a cells [63]. Functional characterization of Arid3a by identifying critical downstream target genes will ultimately be required to fully understand the function of this pathway in controlling B-1a cell development.…”

Section: Transcriptional Control Of B-1a Cell Developmentmentioning

confidence: 89%

Control of B-1a cell development by instructive BCR signaling

Kreslavsky

Wong

Fischer

et al. 2018

Current Opinion in Immunology

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B-1a cells remain one of the most enigmatic lymphocyte subsets. In this review, we discuss recent advances in our understanding of the development of these cells and their regulation by the transcription factors Bhlhe41 and Arid3a as well as by the RNA-binding protein Lin28b. A large body of literature supports an instructive role of BCR signaling in B-1a cell development and lineage commitment, which is initiated only after signaling from an autoreactive BCR. While both fetal and adult hematopoiesis can generate B-1a cells, the contribution of adult hematopoiesis to the B-1a cell compartment is low under physiological conditions. We discuss several models that can reconcile the instructive role of BCR signaling with this fetal bias in B-1a cell development.

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“…ARID3B binds with ARID3A and KDM4C to form the ARID3B-complex. The ARID3B-complex plays a vital role in cell proliferation by transcriptional regulation of stemness genes including HMGA1, c-MYC, vascular endothelial growth factor A (VEGF-A), and Wnt family member 1 (WNT1) [18,34,[55][56][57][58][59]. ARID3B knockout in immortalized first trimester human trophoblast cells results in reduced proliferation of these cells [18].…”

Section: Introductionmentioning

confidence: 99%

Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

Ali

Stenglein

Spencer

et al. 2020

IJMS

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LIN28 inhibits let-7 miRNA maturation which prevents cell differentiation and promotes proliferation. We hypothesized that the LIN28-let-7 axis regulates proliferation-associated genes in sheep trophectoderm in vivo. Day 9-hatched sheep blastocysts were incubated with lentiviral particles to deliver shRNA targeting LIN28 specifically to trophectoderm cells. At day 16, conceptus elongation was significantly reduced in LIN28A and LIN28B knockdowns. Let-7 miRNAs were significantly increased and IGF2BP1-3, HMGA1, ARID3B, and c-MYC were decreased in trophectoderm from knockdown conceptuses. Ovine trophoblast (OTR) cells derived from day 16 trophectoderm are a useful tool for in vitro experiments. Surprisingly, LIN28 was significantly reduced and let-7 miRNAs increased after only a few passages of OTR cells, suggesting these passaged cells represent a more differentiated phenotype. To create an OTR cell line more similar to day 16 trophectoderm we overexpressed LIN28A and LIN28B, which significantly decreased let-7 miRNAs and increased IGF2BP1-3, HMGA1, ARID3B, and c-MYC compared to control. This is the first study showing the role of the LIN28-let-7 axis in trophoblast proliferation and conceptus elongation in vivo. These results suggest that reduced LIN28 during early placental development can lead to reduced trophoblast proliferation and sheep conceptus elongation at a critical period for successful establishment of pregnancy.

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A Role for the Transcription Factor Arid3a in Mouse B2 Lymphocyte Expansion and Peritoneal B1a Generation

Cited by 10 publications

References 21 publications

Crucial Role of Increased Arid3a at the Pre-B and Immature B Cell Stages for B1a Cell Generation

Crucial Role of Increased Arid3a at the Pre-B and Immature B Cell Stages for B1a Cell Generation

Control of B-1a cell development by instructive BCR signaling

Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

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