Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Turumi-ku, Kanagawa 230-0045, Japan.
J Exp Med. 2011 Jul 4;208(7):1447-57. doi: 10.1084/jem.20102665. Epub 2011 Jun 27.
CIN85, an adaptor protein which binds the C-terminal domain of tyrosine phosphorylated Cbl and Cbl-b, has been thought to be involved in the internalization and subsequent degradation of receptors. However, its physiological function remains unclear. To determine its role in B cells, we used Mb1-cre to generate mice with a B cell-specific deletion of CIN85. These mice had impaired T cell-independent type II antibody responses in vivo and diminished IKK-β activation and cellular responses to B cell receptor (BCR) cross-linking in vitro. Introduction of a constitutively active IKK-β construct corrected the defective antibody responses as well as cellular responses in the mutant mice. Together, our results suggest that CIN85 links the BCR to IKK-β activation, thereby contributing to T cell-independent immune responses.
CIN85 是一种衔接蛋白，能够与酪氨酸磷酸化的 Cbl 和 Cbl-b 的 C 末端结构域结合，被认为参与了受体的内化和随后的降解。然而，其生理功能尚不清楚。为了确定其在 B 细胞中的作用，我们使用 Mb1-cre 生成了 B 细胞特异性敲除 CIN85 的小鼠。这些小鼠在体内表现出 T 细胞非依赖型 II 型抗体应答受损，体外 IKK-β 激活和细胞对 B 细胞受体 (BCR) 交联的应答减弱。引入组成性激活的 IKK-β 构建体可纠正突变小鼠的缺陷抗体应答和细胞应答。总之，我们的结果表明 CIN85 将 BCR 与 IKK-β 的激活联系起来，从而有助于 T 细胞非依赖型免疫应答。
