Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells
Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells
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DOI：
10.1016/j.bbrc.2013.11.029
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发表时间：
2014-01-10
影响因子：
3.1
通讯作者：
Ishii, Naoto
中科院分区：
文献类型：
--
作者：
Nagata, Takayuki;Murata, Kazuko;Ishii, Naoto
肝细胞生长因子 (HGF) 调节的酪氨酸激酶底物 (Hrs) 是一种囊泡分选蛋白，充当运输 (ESCRT) 所需的内体分选蛋白之一。 Hrs 通过其泛素相互作用基序 (UIM) 与泛素化蛋白结合，有助于泛素化膜蛋白的溶酶体转运和降解。然而，人们对体内 B 细胞功能与 ESCRT 蛋白之间的关系知之甚少。在这里，我们使用 B 细胞特异性 Hrs 缺陷 (Hrs(flox/flox);mb1(cre/+):Hrs-cKO) 小鼠（使用 cre-LoxP 重组系统生成）检查了 Hrs 在 B 细胞发育和功能中的免疫作用。 B细胞中的hrs缺陷显着降低了体内T细胞依赖性抗体的产生，并损害了体外用抗IgM单克隆抗体处理的B细胞的增殖，但用LPS则没有。尽管 Hrs-cKO 小鼠骨髓中 B 细胞的早期发育正常，但 Hrs-cKO 小鼠脾脏中外周移行 B 细胞和边缘区 B 细胞的数量显着减少。这些结果表明Hrs在B淋巴细胞的外周发育和生理功能中发挥着重要作用。 (C) 2013 Elsevier Inc. 保留所有权利。
Hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) is a vesicular sorting protein that functions as one of the endosomal-sorting proteins required for transport (ESCRT). Hrs, which binds to ubiquitinated proteins through its ubiquitin-interacting motif (UIM), contributes to the lysosomal transport and degradation of ubiquitinated membrane proteins. However, little is known about the relationship between B-cell functions and ESCRT proteins in vivo. Here we examined the immunological roles of Hrs in B-cell development and functions using B-cell-specific Hrs-deficient (Hrs(flox/flox);mb1(cre/+):Hrs-cKO) mice, which were generated using a cre-LoxP recombination system. Hrs deficiency in B-cells significantly reduced T-cell-dependent antibody production in vivo and impaired the proliferation of B-cells treated in vitro with an anti-IgM monoclonal antibody but not with LPS. Although early development of B-cells in the bone marrow was normal in Hrs-cKO mice, there was a significant decrease in the number of the peripheral transitional B-cells and marginal zone B-cells in the spleen of Hrs-cKO mice. These results indicate that Hrs plays important roles during peripheral development and physiological functions of B lymphocytes. (C) 2013 Elsevier Inc. All rights reserved.