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Updated: Jun 6, 2026
09:02
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and
Cosmas C Giallourakis1, Andrew Franklin, Chunguang Guo
1Department of Genetics, The Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Summary
The V(H)-D intergenic region controls immunoglobulin heavy-chain (IgH) gene accessibility for V(D)J recombination. Deleting this region activates transcription and IgH rearrangement in T cells.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Immunoglobulin (Ig) and T-cell receptor (TCR) genes assemble via V(D)J recombination, initiated by RAG1/2 endonuclease.
- This process involves joining variable (V), diversity (D), and joining (J) gene segments, crucial for B and T cell development.
- Recombination is regulated by controlling accessibility of gene segments to RAG1/2 activity.
Purpose of the Study:
- To investigate the role of the intergenic region between V(H) and D gene segments in controlling IgH V(D)J recombination.
- To elucidate the regulatory elements within this intergenic region that influence gene segment accessibility and transcription.
Main Methods:
- Deletion of the 100-kb intergenic region between V(H) and D clusters in mice, creating ΔV(H)-D alleles.
- Analysis of sense and antisense transcription from the IgH locus in developing B and T cells.
- Assessment of V(D)J recombination frequencies in B and T lymphocytes with the deleted intergenic region.
Main Results:
- Deletion of the V(H)-D intergenic region led to increased sense and antisense transcription from the D cluster in both B and T cells.
- Antisense transcripts extended into proximal V(H) segments, influencing accessibility.
- In T cells, this transcriptional activation correlated with increased IgH D-to-J(H) and V(H)-to-DJ(H) rearrangement.
Conclusions:
- The V(H)-D intergenic region plays a critical role in silencing germ-line transcription from the IgH D cluster.
- Elements within this region regulate accessibility of IgH gene segments for V(D)J recombination, particularly in T cells.
- Modulation of transcription by the intergenic region influences the targeting and efficiency of V(D)J recombination.
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