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Updated: May 1, 2026
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
Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple
Benjamin Thiele1, Marie Kloster1, Malik Alawi2
1University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum, University Cancer Center Hamburg, Department of Oncology, Hematology, Bone Marrow Transplantation with Section Pneumology, Hamburg, Germany;
Insights
This study found no evidence of pre-switch B cells in myeloma patients. Instead, malignant plasma cells circulate in the blood, potentially spreading the disease.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- The origin of myeloma progenitor cells is debated.
- Previous studies suggested pre-switch B cells are involved in myeloma.
Purpose of the Study:
- To investigate the identity of myeloma progenitor cells.
- To determine if pre-switch B cells contribute to myeloma.
Main Methods:
- Screening peripheral blood B cell repertoires using next-generation sequencing.
- Analyzing immunoglobulin (Ig) rearrangements in myeloma patients.
Main Results:
- Absence of pre-switch clonotypic B cells in all 12 patients.
- Detection of clonotypic rearrangements in post-switch B cells of active myeloma patients.
- Correlation between circulating malignant plasma cells (M-PCs) and disease activity.
Conclusions:
- Pre-switch B cells do not contribute to myeloma.
- Circulating M-PCs are present in active myeloma and may drive disease spread.
- Evidence of ongoing clonal evolution in M-PCs.
Abstract:
The identity of the proliferative compartment of myeloma progenitor cells remains a matter of debate. Polymerase chain reaction-based studies suggested pre-switch "clonotypic" B cells sharing the immunoglobulin (Ig) rearrangement of the malignant plasma cell (M-PC), to circulate in the blood and possess stem cell-like properties. Here, we disprove this hypothesis. We screened peripheral blood IgM, IgG, and IgA repertoires of myeloma patients for the clonotypic rearrangement by next-generation sequencing. None of 12 cases showed pre-switch clonotypic transcripts. In the post-switch IgG/IgA repertoires, however, the clonotypic rearrangement was detected at high frequency in 6 of 8 patients with active disease, whereas it was undetectable after treatment, correlating with flow cytometric presence or absence of circulating M-PCs. Minor subclones with alternative post-switch isotypes suggested ongoing switch events and clonal evolution at the M-PC level. Our findings consistently show an absence of pre-switch clonotypic B cells, while M-PCs circulate in the peripheral blood and may contribute to spreading of the disease.
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