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Expression data for resting and activated B and T cells

ABSTRACT: The IgH locus encodes for part of the antibody exposed by B cells and is important for the immune system. In B cells, one allele produces protein, the other must remain silenced. It was proposed that both alleles reside in different nuclear compartments and that this is important to maintain mono-allelic productivity. Here we challenge this concept. We provide detailed genome-wide contact maps, which show that IgH adopts different nuclear locations in immune versus other cells but also demonstrate that in B cells both alleles reside in the same environment. Nuclear positioning is therefore not important to maintain allelic exclusion. We did a gene expression analysis on resting (Day 0) and in vitro activated (Day 4) B and T cells in triplicate

ORGANISM(S): Mus musculus

PROVIDER: GSE46865 | GEO | 2013/06/01

SECONDARY ACCESSION(S): PRJNA202870

REPOSITORIES: GEO

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Expression data for resting and activated B and T cells

Project description:The IgH locus encodes for part of the antibody exposed by B cells and is important for the immune system. In B cells, one allele produces protein, the other must remain silenced. It was proposed that both alleles reside in different nuclear compartments and that this is important to maintain mono-allelic productivity. Here we challenge this concept. We provide detailed genome-wide contact maps, which show that IgH adopts different nuclear locations in immune versus other cells but also demonstrate that in B cells both alleles reside in the same environment. Nuclear positioning is therefore not important to maintain allelic exclusion. We did a gene expression analysis on resting (Day 0) and in vitro activated (Day 4) B and T cells in triplicate Splenic B cells and T cells were separately isolated from spleen, using magnetic activated cell sorting, and activated in vitro for 4 days

2013-06-01 | E-GEOD-46865 | biostudies-arrayexpress

Allele specific analysis of the immunoglobulin heavy chain locus by simultaneous analysis of the productive and the non-productive allele through paired-end 4C sequencing analysis in mature B cells

Project description:In developing B cells the immunoglobulin heavy chain (IgH) locus is thought to move from repressive to permissive chromatin compartments to facilitate its scheduled rearrangement. In mature B cells, maintenance of allelic exclusion has been proposed to involve recruitment of the non-productive IgH allele to pericentromeric heterochromatin. Here we used an allele-specific chromosome conformation capture combined with sequencing (4C-seq) approach to unambigously follow the individual IgH alleles in mature B lymphocytes. Despite their physical and functional difference, productive and non-productive IgH alleles in B cells and unrearranged IgH alleles in T cells share many chromosomal contacts and largely reside in active chromatin. In brain, however, the locus resides in a different, repressive environment. We conclude that IgH adopts a lymphoid-specific nuclear location that is however unrelated to maintenance of allelic exclusion. We additionally find that in mature B cells - but not in T cells – the distal VH regions of both IgH alleles position themselves away from active chromatin. This, we speculate, may help to restrict enhancer activity to the productively rearranged VH promoter element. Allele specific analysis of the nuclear organization of the IgH locus in resting and activated B cells and T cells and fetal brain cells

2013-06-01 | E-GEOD-47128 | biostudies-arrayexpress

Allele specific analysis of the immunoglobulin heavy chain locus by simultaneous analysis of the productive and the non-productive allele through paired-end 4C sequencing analysis in mature B cells

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Influence of immunoglobulin genotypes on the elicitation of SARS CoV-2 neutralizing antibodies

Project description:The human immunoglobulin heavy chain (IGH) locus is exceptionally polymorphic with high allelic diversity of variable (V) genes and structural variation affecting large regions of the locus. Thus, our germline IGHV gene and allele content is highly personal, which may influence how we respond to infections and vaccinations. Here, we coupled individualized IGHV genotyping with the isolation of monoclonal antibodies against the SARS-CoV-2 spike, focusing on the IGHV1-69 and IGHV3-30 group of genes, which were over-represented in spike-specific B cells. These genes are characterized by both allelic and copy number variations, making them ideal for expanding our understanding of inter-individual differences in antigen-specific antibody responses. We found that for the IGHV1-69*20-using CAB-I47 antibody, the allele usage was critical as germline reversion to other, highly similar, IGHV1-69 alleles abolished the neutralizing activity. Our results demonstrate that as little as single nucleotide differences between different alleles can greatly influence the biological response.

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2019-05-08 | GSE115492 | GEO

Allelic specificity of IGH-DUX4 translocation in acute lymphoblastic leukemia (ALL) [Hi-C]

Project description:In Nalm6, mono-allelic interaction between IGH enhancer and IGH promoter was found from Hi-C data.

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Allelic specificity of IGH-DUX4 translocation in acute lymphoblastic leukemia (ALL) [ATAC-seq]

Project description:In Nalm6, allelic imbalance was found at IGH-DUX4 translocation locus from ATAC-seq data.

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Allelic specificity of IGH-DUX4 translocation in acute lymphoblastic leukemia (ALL) [H3K27ac ChIP-seq]

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Project description:Three-dimensional genome organization orchestrates recombination and transcription of immunoglobulin heavy chain (Igh) genes. The structure of wild type (WT) alleles includes a prominent architectural stripe that extends from a cluster of CTCF binding elements at the 3’ end of the locus (3’CBE), suggesting interactions of this end with sequences throughout the 2Mb Igh TAD. Here we elucidate interplay between regulatory elements located in the 3’Igh domain (260 kb) that impact the stripe. The CTCF-lacking intronic enhancer, Eì, promotes stripe formation and tethers sub-TADs between flanking CTCF-bound 3’CBE and IGCR1. Substituting Eì with an EF1á promoter in different orientations partially recapitulates epigenetic features of WT Igh alleles, including active histone modifications, sub-TAD formation and interactions with the 3’CBE, but does not restore VDJ recombination. Loss of IGCR1 increases the stripe while inverting the 3’CBE redirects the stripe away from the Igh locus. However, inverted 3’CBE continue to serve as a boundary against aberrant activation of genes outside the Igh domain by Eì. Our observations provide insights into mechanisms by which regulatory elements modulate chromatin structure and stripe formation.

2025-01-21 | GSE280719 | GEO

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