THE CD40 LIGAND, GP39, IS DEFECTIVE IN ACTIVATED T-CELLS FROM PATIENTS WITH X-LINKED HYPER-IGM SYNDROME
THE CD40 LIGAND, GP39, IS DEFECTIVE IN ACTIVATED T-CELLS FROM PATIENTS WITH X-LINKED HYPER-IGM SYNDROME
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DOI：
10.1016/0092-8674(93)90668-g
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发表时间：
1993-01-29
期刊：
影响因子：
64.5
通讯作者：
OCHS, HD
中科院分区：
文献类型：
--
作者：
ARUFFO, A;FARRINGTON, M;OCHS, HD
CD 40受体在B细胞应答中的重要作用使我们研究了gp 39-CD 40相互作用在一组抗体产生缺陷的原发性免疫缺陷患者中的作用。在这里，我们报告，高IgM综合征（HIM）患者有缺陷的gp 39-CD 40相互作用。来自HIM患者的B细胞表达功能性CD 40，但其T细胞不结合CD 40-IG。这些患者表达正常水平的gp 39 mRNA，但由于gp 39胞外结构域的突变，这些mRNA编码有缺陷的gp 39蛋白。含有这些突变的gp 39的可溶性重组形式不能结合CD 40并驱动正常的B细胞增殖。编码gp 39的基因被定位到Xq 26，这是X染色体区域，负责HIM的基因先前已被定位。这些数据表明，gp 39的缺陷是X连锁HIM的基础。
The prominent role of the CD40 receptor in B cell responses led us to investigate the role of the gp39-CD40 interaction in a group of primary immunodeficient patients with defective antibody production. Here we report that patients with hyper-IgM syndrome (HIM) have a defective gp39-CD40 interaction. B cells from HIM patients express functional CD40, but their T cells do not bind CD40-Ig. These patients expressed normal levels of gp39 mRNA, but these mRNAs encode defective gp39 proteins owing to mutations in the extracellular domain of gp39. Soluble recombinant forms of gp39 containing these mutations were unable to bind CD40 and drive normal B cell proliferation. The gene encoding gp39 was mapped to Xq26, the X chromosome region where the gene responsible for HIM had previously been mapped. These data suggest that a defect in gp39 is the basis of X-linked HIM.