TY - JOUR
T1 - Soluble and membrane-bound TNF-α are involved in the cytotoxic activity of B cells from tumor-bearing mice against tumor targets
AU - Lopez-Cepero, Mayra
AU - Garcia-Sanz, Jose A.
AU - Herbert, Lynn
AU - Riley, Richard
AU - Handel, Mary E.
AU - Podack, Eckhard R.
AU - Lopez, Diana M.
PY - 1994/4/1
Y1 - 1994/4/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8144919
AN - SCOPUS:0028181866
VL - 152
SP - 3333
EP - 3341
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -