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Immunoglobulin V gene expression in CD5 B-cell malignancies
T J Kipps1, L Z Rassenti, S Duffy
1Department of Medicine, University of California, San Diego, La Jolla 92093-0945.
Annals of the New York Academy of Sciences
|May 4, 1992
Summary
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) involve CD5 B cells. Studies suggest non-random gene rearrangement and selection shape the antibody repertoire in these B-cell malignancies.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are CD5 B-cell malignancies.
- Distinguishing subtypes requires immunophenotypic and clinicopathologic data.
- Neoplastic cells coexpress surface immunoglobulin (Ig) with cross-reactive idiotypes (CRIs).
Purpose of the Study:
- To investigate the role of Ig V gene rearrangement and selection in CLL/SLL.
- To understand the origin of CRIs in CLL/SLL B-cell malignancies.
- To explore potential antigen selection mechanisms in CLL/SLL autoantibodies.
Main Methods:
- Analysis of immunophenotypic and clinicopathologic data.
- Investigation of Ig V gene rearrangements, including Humkv325 and VH1 genes.
- Comparison of Ig expressed by malignant and non-malignant B cells.
Main Results:
- CRIs (e.g., 17.109, G6) are frequently found on CLL/SLL cells.
- Biased Ig V gene rearrangement and selection are evident, with minimal somatic mutation.
- Specific Ig rearrangements (Humkv325, VH1) and CDR3 restrictions are observed in CLL/SLL.
Conclusions:
- Non-stochastic Ig V gene rearrangement influences the Ig repertoire in CLL/SLL.
- The autoantibodies in CLL/SLL may be selected based on antigen-binding activity.
- These findings suggest a role for antigen selection in the pathogenesis of CLL/SLL.