Abnormal binding pattern and composition of the NF-kappaB complex components are involved in increased TNF-alpha production by tumor bearer B cells.

B lymphocytes from mammary tumor bearers are cytotoxic against tumor targets and produce TNF-alpha. A greater stability of RNA and a decreased rate of RNA degradation was observed in B cells of tumor bearers compared to those of normal mice. The TNF-alpha promoter contains regions that bind NF-kappaB, which regulate the rate of transcription. Supershift assays for the NF-kappaB region showed that there are p50-p65 heterodimers and p50 homodimers in the nuclear extracts of the two types of B cells, while those from tumor bearers lack the c-Rel component that is present in normal B cells. These results indicate that abnormalities in binding and composition of the NF-kappaB complexes may be involved in the increased TNF-alpha production by B cells of tumor bearers.