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Tumorigenesis mediated by an antigen receptor
H M Jäck1, G Beck-Engeser, G Lee
1Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Summary
B-cell lymphomas in B/W mice are driven by antigen receptors. Continuous stimulation of surface IgM by endogenous antigens promotes tumor cell growth, indicating antigen receptor-mediated tumorigenesis.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- B-cell lymphomas in B/W mice share nearly identical immunoglobulin heavy chain variable regions.
- The NYC B lymphoma cell line expresses IgM that binds a viral antigen produced by the tumor cells.
Purpose of the Study:
- To investigate the role of surface immunoglobulin (IgM) and antigen interaction in the growth and tumorigenesis of B-cell lymphomas in B/W mice.
- To determine if continuous antigen receptor stimulation is essential for B lymphoma cell proliferation.
Main Methods:
- Comparative analysis of immunoglobulin heavy chain variable regions in B-cell tumors.
- Assessment of IgM binding to viral antigens.
- Screening for immunoglobulin-negative variants in cultured NYC cells.
- Evaluation of cell culture growth capacity in relation to surface immunoglobulin synthesis.
Main Results:
- NYC IgM exhibits binding to a tumor-specific viral antigen.
- No immunoglobulin-negative variants were detected in NYC cells despite extensive screening.
- NYC cells lose their capacity for in vitro growth when surface immunoglobulin synthesis is inhibited.
Conclusions:
- The interaction between endogenous antigens and surface IgM acts as a continuous growth stimulus for B lymphoma cells.
- Antigen receptors are implicated as the mediators of B lymphoma tumorigenesis in B/W mice.
- Surface immunoglobulin expression and antigen binding are critical for the sustained proliferation of these B-cell tumors.