Effect of the ornithine decarboxylase inhibitor α,α-difluoromethylornithine on phorbol diester-induced inhibition of murine B lymphocyte differentiation

L. D. Schuman, C. S. Baxter, T. M. Petro

Research output: Contribution to journalArticle

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Abstract

The tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits the differentiation of murine B lymphocytes to antibody-producing plasma cells, in unfractionated spleen cell cultures or enriched B lymphocyte cultures. To determine the role of polyamines in TPA-induced inhibition, unfractionated splenic lymphocytes, in culture with antigen, were incubated with α,α-difluoromethylornithine (DFMO, 0.10 mM), an irreversible inhibitor of ornithine decarboxylase (ODC). DFMO prevented the TPA-induced inhibition of antibody forming cell number in a 5-day in vitro immunization procedure as measured by a hemolytic plaque assay. In enriched B lymphocyte cultures, however, DFMO had no comparable effect. DFMO did not prevent TPA-induced inhibition of antibody production in unfractionated spleen cell cultures but itself inhibited the amount of antibody produced. Putrescine (0.1 mM), added on day 4 of immunization, reversed DFMO inhibition of antibody production but did not enable DFMO to prevent the TPA-induced inhibition. These findings suggest that TPA-induced inhibition of plasma cell number can be mediated indirectly through effects on T lymphocytes and/or macrophages or directly through effect on B lymphocytes.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalCancer Letters
Volume47
Issue number1-2
DOIs
Publication statusPublished - Sep 15 1989

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Keywords

  • B cells
  • DFMO
  • antibody response
  • ornithine decarboxylase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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