Punnonen J, Aversa G, Cocks B G, McKenzie A N, Menon S, Zurawski G, de Waal Malefyt R, de Vries J E
Human Immunology Department, DNAX Research Institute, Palo Alto, CA 94304-1104.
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3730-4. doi: 10.1073/pnas.90.8.3730.
Recently the cDNA encoding interleukin 13 (IL-13), a T-cell-derived cytokine, was cloned and expressed. The present study demonstrates that IL-13 induces IgG4 and IgE synthesis by human B cells. IL-13-induced IgG4 and IgE synthesis by unfractionated peripheral blood mononuclear cells and highly purified B cells cultured in the presence of activated CD4+ T cells or their membranes. IL-13-induced IgG4 and IgE synthesis is IL-4-independent, since it was not affected by neutralizing anti-IL-4 monoclonal antibody. Highly purified, surface IgD+ B cells could also be induced to produce IgG4 and IgE by IL-13, indicating that the production of these isotypes reflected IgG4 and IgE switching and not a selective outgrowth of committed B cells. IL-4 and IL-13 added together at optimal concentrations had no additive or synergistic effect, suggesting that common signaling pathways may be involved. This notion is supported by the observation that IL-13, like IL-4, induced CD23 expression on B cells and enhanced CD72, surface IgM, and class II major histocompatibility complex antigen expression. In addition, like IL-4, IL-13 induced germ-line IgE heavy-chain gene transcription in highly purified B cells. Collectively, our data indicate that IL-13 is another T-cell-derived cytokine that, in addition to IL-4, efficiently directs naive human B cells to switch to IgG4 and IgE production.
最近,编码白细胞介素13(IL-13)——一种T细胞衍生的细胞因子——的cDNA被克隆并表达。本研究表明,IL-13可诱导人B细胞合成IgG4和IgE。在活化的CD4+T细胞或其细胞膜存在的情况下,IL-13可诱导未分级的外周血单核细胞和高度纯化的B细胞合成IgG4和IgE。IL-13诱导的IgG4和IgE合成不依赖IL-4,因为它不受中和性抗IL-4单克隆抗体的影响。高度纯化的表面IgD+B细胞也可被IL-13诱导产生IgG4和IgE,这表明这些同种型的产生反映了IgG4和IgE的类别转换,而不是定向B细胞的选择性增殖。以最佳浓度共同添加IL-4和IL-13没有相加或协同作用,这表明可能涉及共同的信号通路。这一观点得到以下观察结果的支持:IL-13与IL-4一样,可诱导B细胞上CD23的表达,并增强CD72、表面IgM和II类主要组织相容性复合体抗原的表达。此外,与IL-4一样,IL-13可诱导高度纯化的B细胞中胚系IgE重链基因转录。总体而言,我们的数据表明,IL-13是另一种T细胞衍生的细胞因子,除IL-4外,它还能有效地引导未成熟的人B细胞转换为产生IgG4和IgE。