The role of tumor necrosis factor-α (TNF-α) in human B cell responses was examined and compared with that of interleukin (IL) 1 by assessing the ability of each cytokine to support proliferation and differentiation. Recombinant TNF-α (rTNF-α) and recombinant IL-1 (rIL-1) each enhanced the generation of immunoglobulin-secreting cells (ISC) in cultures of pokeweed mitogen-stimulated B cells incubated with T cells. To examine the direct effect of rTNF-α and rIL-1 on the responding B cell, highly purified peripheral blood B cells were stimulated with Cowan I staphylococcus aureus (SA). In the absence of T cell factors, proliferation was minimal and there was no generation of ISC. Recombinant IL-2 (rIL-2) supported both responses. Although rTNF-α alone did not support SA-stimulated generation of ISC, it did increase SA-stimulated B cell DNA synthesis by two- to eightfold. In addition, rTNF-α augmented B cell proliferation in rIL-2 supported SA-stimulated cultures. Moreover, rTNF-α enhanced the generation of ISC stimulated by rIL-2 alone or rIL-2 and SA. rIL-1 also augmented DNA synthesis and generation of ISC by B cells stimulated with SA and rIL-2. However, rTNF-α enhanced proliferation and ISC generation in SA + rIL-2 stimulated cultures even when they were supplemented with saturating concentrations of rIL-1. Utilizing a two-stage culture system, it was found that the major effect of rTNF-α was to enhance responsiveness of SA-activated B cells to rIL-2, whereas it exerted only a minimal effect during initial stimulation. These results indicate that TNF-α as well as IL-1 augment B cell responsiveness. Morever, the ability of rTNF-α to enhance B cell responsiveness was not an indirect effect resulting from the induction of IL-1 production by contaminating monocytes, but rather resulted from the delivery of a signal by rTNF-α directly to the responding B cell that promoted both proliferation and differentiation after initial activation. The data therefore indicate that human B cell responsiveness can be independently regulated by the action of two separate monocyte-derived cytokines.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Dec 1 1987|
ASJC Scopus subject areas
- Immunology and Allergy