Pène J, Rousset F, Brière F, Chrétien I, Paliard X, Banchereau J, Spits H, De Vries J E
UNICET, Laboratories for Immunological Research, Dardilly, France.
J Immunol. 1988 Aug 15;141(4):1218-24.
Seven T cell clones were established from mixed leukocyte cultures in which PBMC from two healthy donors and from one patient suffering from the hyper-IgE syndrome were stimulated by the irradiated EBV-transformed B cell lines JY or UD53. Five of seven T cell clones, after activation by co-cultivation with JY or UD53 cells, induced a low degree of IgE production by normal blood B cells. In one experiment in which the normal B cells could activate the T cell clones directly, IgE production was also observed in the absence of the specific stimulator cells. IgE production was also obtained with supernatants of the T cell clones collected 4 to 5 days after activation by their specific stimulator cells. In addition, the supernatants induced IgG, IgA, and IgM synthesis. All seven clones produced variable concentrations of IL-4 and IFN-gamma. The clones FA-28 and BG-39, which failed to induce IgE synthesis, produced, compared with the other clones tested, relatively high quantities of IFN-gamma (4700 and 2500 pg/ml, respectively). These high levels of IFN-gamma accounted for the lack of induction of IgE synthesis, because in the presence of a polyclonal anti-IFN-gamma antiserum, supernatants of FA-10 and BG-39 induced significant IgE production. In addition, the low degree of IgE production induced by supernatants of two other T cell clones (FA28 and BG24) was 15- and 3-fold enhanced, respectively, in the presence of the anti-IFN-gamma antiserum. IgE synthesis by normal B cells was also induced by rIL-4, indicating that IL-4 present in T cell clone supernatants was responsible for induction of IgE production. This notion was supported by the finding that IgE production induced by supernatant of BG-24 was strongly inhibited by a polyclonal anti-IL-4 antiserum. In contrast, IgG and IgA production induced by supernatant of BG-24 were not significantly affected by the anti-IL-4 antiserum. Only a slight inhibition of IgM synthesis was observed. Collectively, our results indicate that both recombinant and naturally produced IL-4 induce normal human B cells to synthesize IgE. However, final IgE production induced by T cell clone supernatants is the net result of the inducing and suppressive effects of IL-4 and IFN-gamma respectively, that are secreted simultaneously by the T cell clones upon activation.
从混合淋巴细胞培养物中建立了7个T细胞克隆，其中来自两名健康供体和一名患有高IgE综合征患者的外周血单个核细胞（PBMC）被经辐照的EBV转化B细胞系JY或UD53刺激。7个T细胞克隆中的5个，在与JY或UD53细胞共培养激活后，可诱导正常血液B细胞产生低水平的IgE。在一项正常B细胞可直接激活T细胞克隆的实验中，在无特异性刺激细胞的情况下也观察到了IgE的产生。用其特异性刺激细胞激活4至5天后收集的T细胞克隆的上清液也能诱导产生IgE。此外，这些上清液还能诱导IgG、IgA和IgM的合成。所有7个克隆均产生不同浓度的IL-4和IFN-γ。未能诱导IgE合成的克隆FA-28和BG-39，与其他测试克隆相比，产生相对较高量的IFN-γ（分别为4700和2500 pg/ml）。这些高水平的IFN-γ导致了IgE合成诱导的缺乏，因为在存在多克隆抗IFN-γ抗血清的情况下，FA-10和BG-39的上清液可诱导显著的IgE产生。此外，在存在抗IFN-γ抗血清的情况下，另外两个T细胞克隆（FA28和BG24）的上清液诱导的低水平IgE产生分别增强了15倍和3倍。重组IL-4也可诱导正常B细胞合成IgE，这表明T细胞克隆上清液中存在的IL-4负责诱导IgE的产生。BG-24上清液诱导的IgE产生被多克隆抗IL-4抗血清强烈抑制，这一发现支持了这一观点。相反，BG-24上清液诱导的IgG和IgA产生不受抗IL-4抗血清的显著影响。仅观察到IgM合成有轻微抑制。总体而言，我们的结果表明，重组IL-4和天然产生的IL-4均可诱导正常人B细胞合成IgE。然而，T细胞克隆上清液诱导的最终IgE产生是T细胞克隆激活后同时分泌的IL-4和IFN-γ的诱导和抑制作用的净结果。
