IL-13 INDUCES PROLIFERATION AND DIFFERENTIATION OF HUMAN B-CELLS ACTIVATED BY THE CD40-LIGAND
IL-13 INDUCES PROLIFERATION AND DIFFERENTIATION OF HUMAN B-CELLS ACTIVATED BY THE CD40-LIGAND
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DOI：
10.1093/intimm/5.6.657
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发表时间：
1993-06-01
影响因子：
4.4
通讯作者：
AVERSA, G
中科院分区：
文献类型：
--
作者：
COCKS, BG;MALEFYT, RD;AVERSA, G
我们从激活的 CD8+T 细胞克隆构建的 cDNA 文库中克隆了人 CD40 配体 (hCD40L)。检测到代表 2.1 kb 和 1.4 kb 克隆的两个 cDNA。两个 cDNA 克隆具有相同的 261 个氨基酸开放阅读框，仅 3' 非翻译末端的长度不同，可能代表在激活的 CD4+ T 细胞克隆中通过 Northern 分析检测到的 2.1 和 1.4 kb mRNA 种类。 hCD40L 转录本也可以在 CD4+ 和 CD8+ TCR Alphata T 细胞、TCR gammadelta T 细胞、自然杀伤细胞、单核细胞、小肠和胎儿胸腺细胞中检测到，但不能在纯化的 B 细胞、胎儿肝脏、胎儿骨髓、大脑、肾脏或心脏中检测到。用hCD40L (COS-7/hCD40L)转染的COS-7细胞诱导人B细胞活化，这通过Epstein-Barr病毒转化的和正常B细胞的同型聚集体的诱导来判断。此外，COS-7/hCD40L 诱导 B 细胞增殖，IL-4 或 IL-13 进一步增强 B 细胞增殖。 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，但不产生 IgA。抗IL-4抗体抑制IL-4和COS-7/hCD40L诱导的B细胞Ig产生，但对IL-13和COS-7/hCD40L诱导的B细胞分化没有影响，表明IL-13和hCD40L独立于IL-4诱导Ig产生，包括同型转换为IgE。 hCD40L 诱导的 B 细胞分化被可溶性 CD40 阻断，证实了 CD40L 特异性参与的需要。总的来说，这些数据表明，人 CD4+ T 辅助细胞表达的 CD40L 和 IL-13 是 T-B 细胞相互作用的重要组成部分，导致 B 细胞增殖、分化和 IgE 转换。然而，hCD40L 的分布表明该分子具有更广泛的功能。
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 alphabeta T cells, TCR gammadelta 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. Collectively, these data indicate that CD40L and IL-13 expressed by human CD4+ T helper cells are important components of T - B cells interactions resulting in B cell proliferation, differentiation and IgE switching. However, the distribution of the hCD40L suggests a broader function of this molecule.