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Updated: Apr 18, 2026
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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
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VH replacement in primary immunoglobulin repertoire diversification
Amy Sun1, Tatiana I Novobrantseva2, Maryaline Coffre1
1Department of Pathology, New York University School of Medicine, New York, NY 10016; and.
Summary
VH replacement, a secondary B-cell receptor gene rearrangement, diversifies the antibody repertoire by modifying productive V(D)J joints before light chain rearrangement. This process does not edit self-reactive antibodies.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- B-cell antigen receptor (BCR) genes assemble from V, D, and J elements via RAG-mediated recombination.
- Secondary V(D)J rearrangement can modify initial Ig rearrangements for repertoire diversification or to correct nonproductive alleles.
Purpose of the Study:
- To characterize the role of VH replacement in primary Ig repertoire diversification.
- To investigate VH replacement in a novel knock-in mouse model mimicking endogenous IgH rearrangement.
Main Methods:
- Utilized a novel knock-in mouse model with a prerearranged IgH locus.
- Analyzed VH replacement in the context of productive V(D)J rearrangements.
Main Results:
- VH replacement modifies productive V(D)J rearrangements to diversify the primary Ig repertoire.
- VH replacement occurs prior to Ig light chain rearrangement.
- VH replacement is not involved in editing self-reactive antibodies.
Conclusions:
- VH replacement is a significant mechanism for diversifying the primary antibody repertoire.
- The timing of VH replacement, before light chain rearrangement, excludes its role in self-reactive antibody editing.
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