Ikizawa K, Kajiwara K, Koshio T, Matsuura N, Yanagihara Y
Clinical Research Centre for Allergy, National Sagamihara Hospital, Japan.
Clin Exp Immunol. 1995 Jun;100(3):383-9. doi: 10.1111/j.1365-2249.1995.tb03710.x.
IL-4 is shown to up-regulate its own receptor (IL-4R) on human lymphocytes, but the functional significance of up-regulated IL-4R is not clear regarding IgE production. This study investigated the possible role of IL-4-induced up-regulation of IL-4R on B cells in the induction of human IgE synthesis by means of antisense strategy. Among three antisense oligodeoxynucleotides designed against the downstream of translation initiation site of IL-4R cDNA, S-oligo 1, complementary to nucleotide 1-24, showed the strongest inhibition of the constitutive expression of IL-4R on Daudi cells. Addition of S-oligo 1 together with IL-4 also decreased the up-regulated but not constitutive levels of IL-4R on peripheral blood B cells without affecting the concomitant enhancement of CD23, CD40, HLA-DR and surface IgM expression, indicating that its effect is specific for IL-4R up-regulation. When S-oligo 1 was added to B cells costimulated with IL-4 and anti-CD40 MoAb, it induced a dose-dependent inhibition of IgE production. This inhibition was accompanied by a decrease in the expression of mature C epsilon transcripts, whereas the accumulation of germ-line C epsilon transcripts was not affected by S-oligo 1. These data suggest that the signal transduction mediated by the up-regulated IL-4R on B cells may be intimately associated with the induction of isotype switching to IgE that leads to mature C epsilon transcription and IgE production.
白细胞介素-4（IL-4）可上调人淋巴细胞上其自身的受体（IL-4R），但上调的IL-4R在免疫球蛋白E（IgE）产生方面的功能意义尚不清楚。本研究采用反义策略，探讨了IL-4诱导B细胞上调IL-4R在人IgE合成诱导中的可能作用。在针对IL-4R cDNA翻译起始位点下游设计的三种反义寡脱氧核苷酸中，与核苷酸1 - 24互补的S-oligo 1对Daudi细胞上IL-4R的组成型表达具有最强的抑制作用。S-oligo 1与IL-4一起添加，也可降低外周血B细胞上IL-4R上调而非组成型表达的水平，且不影响同时出现的CD23、CD40、人类白细胞抗原-DR（HLA-DR）和表面IgM表达的增强，表明其作用对IL-4R上调具有特异性。当将S-oligo 1添加到用IL-4和抗CD40单克隆抗体（MoAb）共刺激的B细胞中时，它可诱导IgE产生的剂量依赖性抑制。这种抑制伴随着成熟Cε转录本表达的降低，而种系Cε转录本的积累不受S-oligo 1影响。这些数据表明，B细胞上上调的IL-4R介导的信号转导可能与向IgE的同种型转换诱导密切相关，该转换导致成熟Cε转录和IgE产生。
