Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Essential role of the transcription factor Bhlhe41 in regulating the self-renewal and BCR repertoire of B-1a cells

ABSTRACT: The innate-like B-1a cells provide a first line of defense against pathogens, and yet little is known about their transcriptional control. Here we identified an essential role of the transcription factor Bhlhe41, with a lesser contribution of Bhlhe40, in controlling late stages of B-1a cell differentiation. Bhlhe41/Bhlhe40 mutant B-1a cells were strongly reduced and had an abnormal cell-surface phenotype and altered B-cell receptor (BCR) repertoire, as exemplified by loss of the phosphatidylcholine-specific Vh12/Vk4 BCR. Expression of a pre-rearranged Vh12/Vk4 BCR failed to rescue the mutant phenotype and revealed enhanced proliferation accompanied with increased cell death, implicating Bhlhe41 in controlling the self-renewal of B-1a cells. Bhlhe41 directly repressed the expression of cell cycle regulators and inhibitors of BCR signaling, while activating pro-survival cytokine signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE93764 | GEO | 2017/01/19

SECONDARY ACCESSION(S): PRJNA362312

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BCR repertoire analysis of wild-type and Cic-null B-1a cells

Project description:Purpose: B-1a cells have a distinct BCR repertoire compared with that of B-2 cells. To examine whether CIC loss affects the BCR repertoire in B-1a cells, we analyzed mRNA sequences of immunoglobulin heavy (Igh) and light (Igk and Igl) chain genes in B-1a cells from 12-week-old control and Cicf/f;Cd19-Cre mice. Methods: Peritoneal cavity B-1a cells (IgM+, CD19+, CD5+, CD43+) were sorted by a MoFlo-XDP (Beckman Coulter). Total RNA was extracted using TRIzol Reagent (GeneAll), according to the manufacturer’s instructions. Long Read iR-Profile Reagent System (iRepertoire) was used to generate NGS libraries covering BCR chains including Igh, Igk, and Igl. Briefly, nested inside and outside primers selectively amplified all V- and C- regions and incorporated communal adaptors. Following clean up, only target amplicons, which contain 5’ and 3’ communal adaptors, were exponentially amplified. Amplified libraries were multiplexed for sequencing on the Illumina Miseq platform. Sequence reads were de-multiplexed according to the barcode sequences. Results: Trimmed reads were mapped to germline V, D and J reference sequences downloaded from the IMGT database. IgH diversity and the usage of variable (V) segments in heavy (Ighv) chain and light (Igkv and Iglv) chain genes were comparable between control and Cic-null B-1a cells. Analysis of non-templated (N)-nucleotide addition at V(D)J junctions revealed that Cic-null B-1a cells have a higher proportion of zero to two N-nucleotides-containing-BCRs than control cells. Conclusions: Our study presents the first comparative BCR repertoire analysis of wild-type and Cic-null B-1a cells. We concluded that CIC deficiency does not dramatically alter the BCR repertoire in B-1a cells.

2021-12-16 | GSE164147 | GEO

BCR heavy and light chain repertoire sequencing of pertitoneal cavity B-1a cells from wild-type and Igll1 knockout mice

Project description:We report that B-1a cells develop in a surrogate light chain independent context. As a consequence, the precursor B-1a cell population avoids a pre-BCR positive selection stage. To confirm that the B-1a cells generated in this manner repersent a bonafide B-1a cell compartment, we did NGS on BCR rearrangements to assess the repertoire diversity. We find that as a whoile, B-1a cell repertoire that develop in Igll1 kncokout mice are similar compared to wild-type. This supports our findings that B-1a cells develop properly in the absence of surrogate light chain.

2018-01-15 | GSE104111 | GEO

Fc receptor-like 6 (FCRL6) defines pre-BCR dependent and independent pathways of natural antibody selection

Project description:B-1a cells produce ‘natural’ antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, and differentiation properties conducive for natural Ab generation Compared to FCRL6- pro B cells, the repressed mitotic, DNA damage repair, and signaling activity of FCRL6+ progenitors, yielded VH repertoires with biased distal Ighv segment accessibility, constrained diversity, and hydrophobic and charged CDR-H3 sequences. Beyond nascent autoreactivity, VH11 productivity, which predominates phosphatidylcholine-specific B-1a B cell receptors (BCRs), was higher for FCRL6+ cells as was pre-BCR formation, which was required for Myc induction and VH11, but not VH12, B-1a development. Thus, FCRL6 revealed unexpected heterogeneity in the developmental origins, regulation, and selection of natural Abs at the pre-BCR checkpoint with implications for autoimmunity and lymphoproliferative disorders.

2020-02-26 | GSE132438 | GEO

BCR repertoire analysis of wild-type and Cic-null B-1a cells

Project description:BCR repertoire analysis of wild-type and Cic-null B-1a cells

| PRJNA689304 | ENA

Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity

Project description:Tissues in multicellular organisms are ‘serviced’ by resident macrophages, which perform both generic and tissue-specific functions. The latter relies on unique tissue-specific molecular programs induced by signals from the microenvironment and executed through a combinatorial action of tissue-specific and broadly expressed transcriptional regulators. Here, we identify the transcription factors Bhlhe40 and Bhlhe41 as novel regulators of alveolar macrophages (AMs) – a population that provides the first line of immune defense and executes homeostatic functions in lung alveoli. In the absence of these factors, AMs exhibited decreased proliferation that resulted in a severe disadvantage of knockout AMs in a competitive setting. Gene expression analyses revealed a broad cell-intrinsic footprint of Bhlhe40/Bhlhe41-deficiency manifested by a downregulation of AM signature genes and induction of signature genes of other macrophage lineages. Genome-wide characterization of Bhlhe40 DNA binding suggested that these transcription factors directly repress the expression of lineage-inappropriate genes in AMs. Taken together, these results identify Bhlhe40 and Bhlhe41 as key regulators of AM self-renewal and guardians of their identity.

2019-07-30 | GSE135018 | GEO

BCR repertoire of B cells with distinct developmental timings

Project description:B cells are known to have different properties and BCR repertoires depending on the time of development. Our objective is to investigate the BCR repertoire of B cells across embryonic, neonatal, and adult stages, particularly in cells with a RAG2 expression history. We focus on sequencing and analyzing the immunoglobulin heavy chain (IGH) genes of these cells to understand their BCR diversity and specificity. Additionally, we explore the relationship between B-1a cells and bone marrow IgM+ plasmablasts/plasma cells, aiming to shed light on the development and function of B-1a cells in the immune system.

2023-12-17 | GSE250175 | GEO

Global gene expression changes between PTIP KO and control PerC B-1a cells

Project description:B cel receptor (BCR) signaling and downstream NF-kB activity are crucial for the generation and activation of innate-like B-1 and conventional B-2 B cells, yet the molecular requirements for these signaling pathways are not fully understood. We used microarray analysis to detail the global gene expression differences underlying the developmental phenotype of B-1a cells associated with defciency in the PTIP chromatin regulator protein.

2017-05-02 | GSE98402 | GEO

Enterococcus mundtii 1A strain:1A

Project description:Enterococcus mundtii 1A strain:1A Genome sequencing

| PRJNA172933 | ENA

BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein

Project description:Coordinated BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. Persistence of oncogenic p27 functions despite effective inhibition of BCR-ABL1 may contribute to resistance to tyrosine kinase inhibitors. BCR-ABL1 induced p27 versus knockout, controlling with Empty vector p27 versus knock out

2014-10-08 | E-GEOD-59168 | biostudies-arrayexpress

Escherichia coli 1A strain:1A

Project description:Escherichia coli 1A strain:1A Genome sequencing and assembly

| PRJNA224231 | ENA