Mutations of the Igbeta gene cause agammaglobulinemia in man.
Mutations of the Igbeta gene cause agammaglobulinemia in man.
复制标题
DOI：
10.1084/jem.20070264
复制
发表时间：
2007-09-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
无丙种球蛋白血症是一种罕见的原发性免疫缺陷，其特征为骨髓中B细胞发育的早期阻滞，导致外周B细胞缺失和免疫球蛋白血清水平低/缺失。到目前为止，在85-90%的无丙种球蛋白血症患者中发现了Btk、μ重链、替代轻链、IGα和B细胞连接体的突变。我们报告了第一例由IGβ纯合无义突变引起的无丙种球蛋白血症患者，Igβ是一种跨膜蛋白，作为前BCR复合物的一部分与IGα相关。使用果蝇S2 Schneider细胞的转染实验表明，突变体IGβ不再能够与IGα结合，并且BCR复合物在细胞表面的组装被废除。通过患者骨髓的免疫荧光分析进一步证明了IGβ对人B细胞发育的重要作用，其显示在前B向前B转化时B细胞发育完全阻断。这些结果表明，IGβ基因突变可导致人类无丙种球蛋白血症。
Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, μ heavy chain, surrogate light chain, Igα, and B cell linker have been found in 85–90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igβ, which is a transmembrane protein that associates with Igα as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igβ is no longer able to associate with Igα, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igβ for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igβ can cause agammaglobulinemia in man.