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Antigen selection in human lymphomagenesis
D W Bahler1, A D Zelenetz, T T Chen
1Department of Medicine, Stanford University Medical Center, California 94305.
Cancer Research
|October 1, 1992
Summary
Antigen selection appears crucial for the growth of follicular lymphomas, a type of B-cell cancer. Mutations in tumor genes suggest this selection drives clonal evolution and survival.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Surface immunoglobulin is vital for normal B-cell development.
- The role of surface immunoglobulin in B-cell malignancies, like follicular lymphoma, is not well understood.
- Follicular lymphomas resemble germinal center B-cells, which rely on antigen selection for survival.
Purpose of the Study:
- To investigate the role of antigen selection in the growth and evolution of human follicular lymphomas.
- To analyze mutations in immunoglobulin heavy chain variable genes in follicular lymphoma cases.
Main Methods:
- Cloning and sequencing of immunoglobulin heavy chain variable genes from two follicular lymphoma cases.
- Cloning and sequencing of germ line variable gene counterparts from the same patients.
- Comparative analysis of tumor-derived and germ line sequences to identify mutations.
Main Results:
- Significant mutations were identified in the variable genes of follicular lymphoma cells compared to germ line.
- These mutations accumulated during lymphoma expansion and growth.
- Mutation distribution suggests positive selection, likely driven by antigen contact.
Conclusions:
- Antigen selection is likely a key factor in the growth and clonal evolution of follicular lymphomas.
- Understanding these mechanisms could inform future therapeutic strategies for B-cell malignancies.