Jelinek D F, Lipsky P E
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Health Science Center, Southwestern Medical School, Dallas 75235.
J Immunol. 1987 Nov 1;139(9):2970-6.
The role of tumor necrosis factor-alpha (TNF-alpha) 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-alpha (rTNF-alpha) 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-alpha 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-alpha 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-alpha augmented B cell proliferation in rIL-2 supported SA-stimulated cultures. Moreover, rTNF-alpha 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-alpha 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-alpha 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-alpha as well as IL-1 augment B cell responsiveness. Moreover, the ability of rTNF-alpha 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-alpha 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.
通过评估肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）1支持增殖和分化的能力，研究并比较了它们在人类B细胞反应中的作用。重组TNF-α（rTNF-α）和重组IL-1（rIL-1）均可增强与T细胞一起培养的商陆有丝分裂原刺激的B细胞培养物中免疫球蛋白分泌细胞（ISC）的生成。为了研究rTNF-α和rIL-1对反应性B细胞的直接作用，用考恩I型金黄色葡萄球菌（SA）刺激高度纯化的外周血B细胞。在没有T细胞因子的情况下，增殖极少，也没有ISC生成。重组IL-2（rIL-2）支持这两种反应。尽管单独的rTNF-α不支持SA刺激的ISC生成，但它确实使SA刺激的B细胞DNA合成增加了2至8倍。此外，rTNF-α增强了rIL-2支持的SA刺激培养物中的B细胞增殖。而且，rTNF-α增强了单独的rIL-2或rIL-2与SA刺激的ISC生成。rIL-1也增强了SA和rIL-2刺激的B细胞的DNA合成和ISC生成。然而，即使在补充了饱和浓度的rIL-1的情况下，rTNF-α仍能增强SA + rIL-2刺激培养物中的增殖和ISC生成。利用两阶段培养系统发现，rTNF-α的主要作用是增强SA激活的B细胞对rIL-2的反应性，而在初始刺激期间其作用极小。这些结果表明TNF-α以及IL-1增强了B细胞反应性。此外，rTNF-α增强B细胞反应性的能力不是由污染的单核细胞诱导产生IL-1所导致的间接效应，而是由rTNF-α直接向反应性B细胞传递信号所致，该信号在初始激活后促进了增殖和分化。因此，数据表明人类B细胞反应性可由两种不同来源自单核细胞的细胞因子的作用独立调节。
