Bリンパ球増殖・分化機構の解明とその異常制御に関する研究

白细胞介素6最初被鉴定为T细胞来源的淋巴因子，其诱导B细胞的最终分化，并且其cDNA被克隆。重组IL-6的研究证实IL-6是B细胞产生抗体分子的必需因子之一。然而，研究表明IL-6不仅作用于B细胞，而且对多种组织和细胞具有广泛的生物学功能。例如，它作为细胞毒性T细胞分化因子作用于T细胞，作为多集落刺激因子作用于造血干细胞，作用于肝细胞以诱导急性期蛋白。它作为骨髓瘤/浆细胞瘤生长因子发挥作用，对患者骨髓瘤细胞的结果表明il-6作为骨髓瘤细胞的自分泌生长因子发挥作用。人IL-6基因转基因小鼠产生浆细胞瘤，证实IL-6在B谱系细胞中的组成性表达参与骨髓瘤/浆细胞瘤的肿瘤发生。同时克隆了IL-6受体的cDNA序列，推导的氨基酸序列表明IL-6受体属于免疫球蛋白超家族。还鉴定了参与IL-6信号转导的第二条多肽链，克隆了淋巴细胞Fcepsilon受体（FcepsilonRII）的cDNA。该序列表明，FcepsilonRII具有独特的结构，其C-末端外和N-末端的一半分子被证明作为IgE结合因子分泌，并参与过敏反应的调节。发现Fc ε RII与B细胞特异性分化抗原CD 23相同。证明了存在两种不同种类的FcepsilonRII，其通过差异RNA剪接机制和通过使用不同的转录起始位点产生。它们在胞质内部分显示出不同，并且它们的表达受到不同的调节。

Interleukin 6 was originally identified as T cell-derived lymphokine which induced final differentiation of B cells and its cDNA was cloned. The study with recombinant IL-6 confirmed that IL-6 was one of the essential factor for B cells to produce antibody molecules. However, the studies demonstrated that IL-6 acted not only on B cells but showed a wide variety of biological functions on varions tissues and cells. For example it acts on T cells as cytotoxic T cell differentiation factor, on hematopoietic stem cells as multi-colony stimulating factor, on hepatocytes to induce acute phase proteins. It functions as myeloma/plasmacytoma growth factor and the result with myeloma cells from patients demonstrated that il-6 functioned as an autocrine growth factor for myeloma cells. Transgenic mice with human IL-6 gene generated plasmacytomas confirming that constitutive expression of IL-6 in B lineage cells in involved in oncogenesis of myeloma/plasmacytoma. The cDNA encoding for IL-6 receptor was also cloned and the deduced amino acid sequence showed that IL-6 receptor belongs to immunoglobulin superfamily. A second polypeptide chain involved for IL-6 signal transduction was also identified.The cDNA for lymphocyte Fcepsilon receptor (FcepsilonRII) was cloned. The sequence showed that FcepsilonRII had an unique structure, its C-terminus outside and N-terminal half of the molecule was shown to secrete as IgE binding factor and to be involved in the regulation of allergic reactions. FcepsilonRII was found to be identical with a B cell specific differentiation antigen, CD23. The presence of two different species of FcepsilonRII which were generated by differential RNA splicing mechanism and by the usage of different transcription initiation sites, was demonstrated. They were shown to be different in their intracytoplasmic portion and their expression was differently regulated.