Soluble and membrane-bound TNF-α are involved in the cytotoxic activity of B cells from tumor-bearing mice against tumor targets

Mayra Lopez-Cepero, Jose A. Garcia-Sanz, Lynn Herbert, Richard Riley, Mary E. Handel, Eckhard R Podack, Diana M. Lopez

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Splenic B cells from BALB/c mice bearing mammary adenocarcinomas are capable of performing Ab-dependent cellular cytotoxicity. Effector-target conjugation after 18 h results in minimal cytoplasmic damage, whereas extensive nuclear disintegration is observed. To determine whether splenic B cells from tumor-bearing mice can effect direct cytotoxicity against tumor cells, L929 and WEHI 164 cells were used as targets. B lymphocytes from tumor-bearing mice, but not from normal animals, were capable of lysing these two types of tumor cells. However, only a low level of cytotoxicity could be detected when the nontumorigenic 3T3 cells were used as targets. To elucidate the mechanism of cytotoxicity of these killer B cells, RNase protection assays were performed using perforin, granzyme A, TNF-α, and lymphotoxin probes. No perforin, granzyme A, or lymphotoxin RNA could be detected in purified preparations of B cells from normal and tumor-bearing mice. B cells from normal mice did not have TNF-α RNA. In contrast, B cells from tumor bearers expressed TNF-α RNA. TNF-α could be detected in supernatants from both unstimulated and stimulated tumor bearers' splenic B cells, as measured by ELISA, and its lytic activity was neutralized by anti-TNF-α Ab. Western blots revealed the presence of TNF-α on the surface of the killer B cells. Paraformaldehyde-fixed B cells from tumor-bearing mice but not from normal animals were able to lyse TNF-α-sensitive tumor targets. This cytotoxicity was neutralized by anti-TNF-α Ab. These results suggest that TNF-α in soluble and membrane-bound forms may be involved in the mechanism of cytotoxicity exerted by B cells from tumor-bearing mice.

Original languageEnglish (US)
Pages (from-to)3333-3341
Number of pages9
JournalJournal of Immunology
Volume152
Issue number7
StatePublished - Apr 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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