Cocks B G, de Waal Malefyt R, Galizzi J P, de Vries J E, Aversa G
DNAX Research Institute for Molecular and Cellular Biology, Inc., Human Immunology Department, Palo Alto, CA 94304-1104.
Int Immunol. 1993 Jun;5(6):657-63. doi: 10.1093/intimm/5.6.657.
We cloned the human CD40 ligand (hCD40L) from a cDNA library constructed from an activated CD8+T cell clone. Two cDNAs representing a 2.1 and a 1.4 kb clone were detected. Both cDNA clones had identical open reading frames of 261 amino acids and differed only in the length of their 3' untranslated ends, and probably represent the 2.1 and 1.4 kb mRNA species detected by Northern analysis in an activated CD4+ T cell clone. hCD40L transcripts could also be detected in CD4+ and CD8+ TCR alpha beta T cells, TCR gamma delta T cells, natural killer cells, monocytes, small intestine, and fetal thymocytes, but not in purified B cells, fetal liver, fetal bone marrow, brain, kidney, or heart. COS-7 cells transfected with hCD40L (COS-7/hCD40L) induced human B cell activation as judged by the induction of homotypic aggregates of Epstein-Barr virus transformed and normal B cells. In addition, COS-7/hCD40L induced B cell proliferation, which was further enhanced by IL-4, or IL-13. IL-13, like IL-4, synergized with the mouse and hCD40L to induce IgM, total IgG, IgG4, and IgE, but not IgA, production by highly purified B cells. Anti-IL-4 antibodies inhibited IL-4 and COS-7/hCD40L induced Ig production by B cells, but had no effect on IL-13 and COS-7/hCD40L induced B cell differentiation, indicating that IL-13 and hCD40L induced Ig production, including isotype switching to IgE, independently of IL-4. hCD40L induced B cell differentiation was blocked by soluble CD40, confirming the requirement for specific engagement of CD40L.(ABSTRACT TRUNCATED AT 250 WORDS)
我们从由活化的CD8⁺T细胞克隆构建的cDNA文库中克隆了人CD40配体（hCD40L）。检测到两个分别代表2.1 kb和1.4 kb克隆的cDNA。这两个cDNA克隆具有相同的261个氨基酸的开放阅读框，仅3'非翻译末端长度不同，可能分别代表在活化的CD4⁺T细胞克隆中通过Northern分析检测到的2.1 kb和1.4 kb mRNA种类。在CD4⁺和CD8⁺TCRαβT细胞、TCRγδT细胞、自然杀伤细胞、单核细胞、小肠和胎儿胸腺细胞中也能检测到hCD40L转录本，但在纯化的B细胞、胎儿肝脏、胎儿骨髓、脑、肾或心脏中未检测到。用hCD40L转染的COS-7细胞（COS-7/hCD40L）可诱导人B细胞活化，这可通过爱泼斯坦-巴尔病毒转化的和正常B细胞的同型聚集来判断。此外，COS-7/hCD40L可诱导B细胞增殖，IL-4或IL-13可进一步增强这种增殖。IL-13与IL-4一样，与小鼠和hCD40L协同作用，诱导高度纯化的B细胞产生IgM、总IgG、IgG4和IgE，但不诱导IgA产生。抗IL-4抗体可抑制IL-4和COS-7/hCD40L诱导的B细胞产生Ig，但对IL-13和COS-7/hCD40L诱导的B细胞分化没有影响，这表明IL-13和hCD40L诱导的Ig产生，包括向IgE的同种型转换，独立于IL-4。hCD40L诱导的B细胞分化被可溶性CD40阻断，证实了CD40L特异性结合的必要性。（摘要截短至250字）
