Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Proc Natl Acad Sci U S A 89: 12198-201 (1992)
Abstract
The human tumor necrosis factor alpha (TNF-alpha) gene encodes a
cytokine whose activities have been implicated in many
immunopathological processes, including the activation and
differentiation of lymphocytes. Originally identified as a monocyte
factor, our studies and those of others have demonstrated that B and T
lymphocytes produce TNF-alpha when stimulated by a variety of inducers.
We report here that TNF-alpha gene transcription is rapidly and highly
induced in three independently derived human Burkitt lymphoma cell
lines, as well as in freshly isolated human splenic B cells, activated
by antibodies to surface immunoglobulin. This burst in TNF-alpha gene
transcription is associated with an induction of TNF-alpha bioactivity
in the culture supernatants from stimulated splenic B cells. Moreover,
induction of TNF-alpha gene transcription by anti-immunoglobulin was
blocked by the immunosuppressants cyclosporin A and FK506. These studies
demonstrate that TNF-alpha production is an early event in B-cell
activation and they establish the efficacy of using immunosuppressants
as probes in dissecting transcriptional activation pathways in human B
cells.
Mesh Headings
Unique Identifier: 93101694
Chemical Identifiers (Names)