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The protooncogene MYC can break B cell tolerance.
Yosef Refaeli1, Kenneth A Field, Brian C Turner
1The G. W. Hooper Foundation and Department of Microbiology and Immunology, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA. refaeliy@njc.org
Summary
Overexpression of the protooncogene MYC in B cells breaks immune tolerance, leading to autoimmune responses and kidney disease. MYC is crucial for initiating and sustaining this loss of tolerance, potentially mimicking cytokine functions.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The protooncogene MYC is involved in lymphoid cell proliferation, programmed cell death, and lymphoid tumor development.
- MYC overexpression is a common feature in many lymphomas.
Purpose of the Study:
- To investigate the role of MYC in immune tolerance within the B cell lineage.
- To determine if MYC overexpression can break self-tolerance and contribute to autoimmune disease and lymphoma genesis.
Main Methods:
- Utilized transgenic mouse models with MYC overexpression in B cells.
- Assessed immune responses to a transgenic autoantigen in the presence of MYC overexpression.
- Analyzed B cell phenotype, autoantibody production, and kidney pathology.
Main Results:
- Vigorous MYC expression in B cells broke immune tolerance to a transgenic autoantigen.
- Responsive B cells exhibited an activated phenotype and produced autoantibodies, causing immune complex kidney disease.
- MYC was essential for both initiating and maintaining the breach of immune tolerance.
Conclusions:
- MYC overexpression in B cells can disrupt immune tolerance, leading to autoimmunity.
- MYC may act as a surrogate for cytokines, influencing B cell proliferation and survival.
- These findings highlight MYC's critical role in B cell responses and its expanded contribution to lymphoma pathogenesis.