The protooncogene MYC can break B cell tolerance.
Details
Serval ID
serval:BIB_37931
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The protooncogene MYC can break B cell tolerance.
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424
Publication state
Published
Issued date
2005
Volume
102
Number
11
Pages
4097-4102
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Abstract
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.
Keywords
Animals, Autoantibodies/immunology, B-Lymphocytes/cytology, B-Lymphocytes/immunology, Cell Division/immunology, Cytokines/immunology, Cytokines/metabolism, Immune Tolerance/genetics, Immune Tolerance/immunology, Mice, Mice, Transgenic, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/immunology, Receptors, Antigen, B-Cell/genetics, Receptors, Antigen, B-Cell/immunology, Time Factors
OAI-PMH
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2007 12:36
Last modification date
20/08/2019 13:26