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Transcriptional repressor BCL-6 immortalizes germinal center-like B cells in the absence of p53 function

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Abstract

Chromosomal rearrangements in non-Hodgkin's B-cell lymphoma implicate BCL-6 as an oncogene, yet direct evidence for BCL-6 acting as an oncogene in B cells has been lacking. Here, we show that BCL-6 can immortalize primary B cells, but only in the absence of p53 tumor suppressor function. The expression of BCL-6 led to greatly increased B-cell proliferation, particularly in response to CD40 stimulation. Furthermore, BCL-6-infected p53-deficient B cells gave rise to immortalized cell lines that could be maintained by CD40 stimulation. We found that in primary mouse B cells, BCL-6 repressed expression of the Blimp-1, p27kip1, and cyclin D2 target genes. BCL-6 did not markedly repress the PDCD2 and BCL-XL target genes. The BCL-6 immortalized cell lines had a phenotype consistent with germinal center B cells, they expressed the germinal center-specific M17 gene, and a significant fraction of the cells stained positive with PNA. Our data indicate that BCL-6 may act to maintain B cells in a germinal center-like state, and repression of Blimp-1 by BCL-6 may be particularly crucial for stabilization of the germinal center phenotype. Our data also suggest that disruption of the p53 pathway may be crucial for the development of BCL-6-expressing B-cell lymphomas.

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Acknowledgements

This work was supported by a V Foundation Scholar Award to ALD. We thank Dr Andrei Thomas-Tikhonenko (University of Pennsylvania) for the kind gift of the pJ11 JH probe.

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Authors and Affiliations

  1. Department of Microbiology and Immunology and The Walther Oncology Center, Indiana University School of Medicine, Indianapolis, 46202, IN, USA

    Saritha Kusam, Farha H Vasanwala & Alexander L Dent

  2. The Walther Cancer Institute, Indianapolis, 46208, IN, USA

    Saritha Kusam, Farha H Vasanwala & Alexander L Dent

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  1. Saritha Kusam
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  2. Farha H Vasanwala
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  3. Alexander L Dent
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Correspondence to Alexander L Dent.

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Kusam, S., Vasanwala, F. & Dent, A. Transcriptional repressor BCL-6 immortalizes germinal center-like B cells in the absence of p53 function. Oncogene 23, 839–844 (2004). https://doi.org/10.1038/sj.onc.1207065

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