Effect of the ornithine decarboxylase inhibitor alpha, alpha-difluoromethylornithine on phorbol diester-induced inhibition of murine B lymphocyte differentiation.
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 alpha, alpha-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.
Schuman
L D
LD
University of Cincinnati Medical Center, Institute of Environmental Health, Ohio 45267-0056.
Baxter
C S
CS
Petro
T M
TM
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects*; D015317:Biogenic Polyamines / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D065108:Ornithine Decarboxylase Inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015317:Biogenic Polyamines; D065108:Ornithine Decarboxylase Inhibitors; D013755:Tetradecanoylphorbol Acetate; D000518:Eflornithine