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SRX7184531: GSM4178028: HTGTS_PB_VK8_34_WT_REP5; Mus musculus; OTHER
1 ILLUMINA (Illumina MiSeq) run: 526,197 spots, 263.1M bases, 166.6Mb downloads

Submitted by: NCBI (GEO)
Study: Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [HTGTS]
show Abstracthide Abstract
During V(D)J recombination RAG proteins introduce DNA double strand breaks (DSBs) adjacent to conserved recombination signal sequences (RSS) that contain either 12- or 23-nucleotide spacer regions. Coordinated cleavage following the “12/23” rule predicts that DSBs at variable (V) gene segments should not exceed the level of breakage at joining (J) segments, thereby ensuring that V regions do not engage in undesirable recombination events with one another. Here we report abundant RAG dependent DSBs at a multitude of V? gene segments within the Ig? locus independent of V-J rearrangement. We discover that a large fraction of V? gene segments are flanked not only by a bone-fide 12 spacer, but also an overlapping, 23 spacer flipped RSS. These compatible pairs of RSS mediate recombination and deletion inside the V? cluster even in the complete absence of J? gene segments, and support a novel recombination center (RC) independent of the conventional J?-centered RC. We propose a model that explains V? gene segment usage by taking into account not only the probability of V-to-J rearrangement but also the surprisingly frequent, evolutionarily conserved intra-V? cluster recombination events. These findings shed light on the diverse molecular strategies that shape the primary antigen receptor repertoires. Overall design: HTGTS profile in abelson-transformed pre-B cells, primary splenic B cells, bone marrow B cells, and human PBMC B cells.
Sample: HTGTS_PB_VK8_34_WT_REP5
SAMN13329315 • SRS5690755 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: Illumina MiSeq
Strategy: OTHER
Source: GENOMIC
Selection: other
Layout: PAIRED
Construction protocol: 10 million of Abelson pre-B cells, primary mouse bone marrow pre-B cells, splenic IgM positive B cells, and human PBMC B cells were used for HTGTS analyses. Primary mouse bone marrow pre-B cells were obtained from 6-12 week old wild-type, C57BL/6 mice with flow cytometry cell sorting on a FACSAria II cell sorter (BD Biosciences) using a combination of anti-B220, anti-CD43, anti-CD24 and anti-IgM antibodies (ThermoFisher/eBioscience) (Lin et al., 2016). IgM positive mature resting B cells were isolated from C57BL/6 mice spleen with anti-CD43 MicroBeads (Miltenyi Biotech). Human peripheral blood B cells were isolated from deidentified, donated PBMC using human B cell isolation kit (STEMCELL Technologies 17954). HTGTS was performed as described (Hu et al., 2015). Genomic DNA was extracted from splenic B cells, isolated B cells from human PBMC, or v-Abl cells arrested in G1 for 2 days by treatment with 3 mM of STI-571. Briefly, 20-50 ug of DNA was fragmented via sonication on a Diagenode bioruptor and subjected to linear PCR amplification with a biotinylated primer. Single-stranded PCR products were purified via Dynabeads MyONE C1 streptavidin beads (Life Technologies, 65002) and ligated to bridge adaptors. Adaptor-ligated products were amplified via nested PCR with indexed locus-specific primers and primer annealed to adaptor. The PCR products were further tagged with Illumina sequencing adaptor sequences, size-selected (fragment size 500 – 1,000 bp) via gel extraction and loaded to Illumina MiSeq for paired-end 250 bp sequencing. For translocation analysis, the standard LAM-HTGTS bioinformatic pipeline was used (Hu et al., 2015).
Experiment attributes:
GEO Accession: GSM4178028
Links:
Runs: 1 run, 526,197 spots, 263.1M bases, 166.6Mb
Run# of Spots# of BasesSizePublished
SRR10495446526,197263.1M166.6Mb2020-01-02

ID:
9437265

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