The Protooncogene MYC Can Break B Cell Tolerance

The protooncogene MYC has been implicated in both the proliferation and programmed cell death of lymphoid cells, and in the genesis of lymphoid tumors. Here, we report that overexpression of MYC, as found in many lymphomas, can break immune tolerance. Mice that would otherwise be tolerant to a trans...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-03, Vol.102 (11), p.4097-4102
Main Authors: Refaeli, Yosef, Field, Kenneth A., Turner, Brian C., Trumpp, Andreas, Bishop, J. Michael
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Apoptosis
Autoantibodies - immunology
Autoimmune diseases
B lymphocytes
B-Lymphocytes - cytology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Biological Sciences
Cell Division - immunology
Cytokines
Cytokines - immunology
Cytokines - metabolism
Cytometry
Gene expression
Immune Tolerance - genetics
Immune Tolerance - immunology
Immunology
Lymphocytes
Lymphoma
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - immunology
Proto-Oncogene Proteins c-myc - metabolism
Receptors, Antigen, B-Cell - genetics
Receptors, Antigen, B-Cell - immunology
T lymphocytes
Time Factors
Transgenes
Tumors
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Summary:The protooncogene MYC has been implicated in both the proliferation and programmed cell death of lymphoid cells, and in the genesis of lymphoid tumors. Here, we report that overexpression of MYC, as found in many lymphomas, can break immune tolerance. Mice that would otherwise be tolerant to a transgenic autoantigen mounted an immune response to the antigen if MYC was vigorously expressed in the B cell lineage. The responsive B cells converted to an activated phenotype and produced copious amounts of autoantibody that engendered immune complex disease of the kidney. MYC was required to both establish and maintain the breach of tolerance. These effects may be due to the ability of MYC to serve as a surrogate for cytokines. We found that the gene could mimic the effects of cytokines on both B cell proliferation and survival and, indeed, was required for those effects. These findings demonstrate a critical role for MYC in the response of B cells to antigen and expand the potential contributions of MYC to the genesis of lymphomas.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0409832102