BCL-6 expression during B-cell activation

David Allman, Ashish Jain, Alex Dent, Randal R. Maile, Thomas Selvaggi, Marilyn R. Kehry, Louis M. Staudt

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12- myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35- fold decrease in BCL-6 mRNA levels. Similar down-regulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin- 2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 mRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression.

Original languageEnglish (US)
Pages (from-to)5257-5268
Number of pages12
JournalBlood
Volume87
Issue number12
StatePublished - Jun 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Allman, D., Jain, A., Dent, A., Maile, R. R., Selvaggi, T., Kehry, M. R., & Staudt, L. M. (1996). BCL-6 expression during B-cell activation. Blood, 87(12), 5257-5268.