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

Saritha Kusam, Farha H. Vasanwala, Alexander Dent

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)839-844
Number of pages6
JournalOncogene
Volume23
Issue number3
DOIs
StatePublished - Jan 22 2004

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Germinal Center
B-Lymphocytes
B-Cell Lymphoma
Oncogenes
Cyclin D2
Genes
Phenotype
Cell Line
Non-Hodgkin's Lymphoma
Cell Proliferation
Neoplasms

Keywords

  • B-cell lymphoma
  • BCL-6
  • CD40
  • Germinal center
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Transcriptional repressor BCL-6 immortalizes germinal center-like B cells in the absence of p53 function. / Kusam, Saritha; Vasanwala, Farha H.; Dent, Alexander.

In: Oncogene, Vol. 23, No. 3, 22.01.2004, p. 839-844.

Research output: Contribution to journalArticle

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