鉴定CD72作为IV类信号素CD100的淋巴细胞受体：一种调节B细胞信号传导的新机制。

Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling.

作者信息

Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T, Matsumoto M, Yoshida K, Yakura H, Pan C, Parnes J R, Kikutani H

机构信息

Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita Osaka 565-0871, Japan.

出版信息

Immunity. 2000 Nov;13(5):621-31. doi: 10.1016/s1074-7613(00)00062-5.

DOI:10.1016/s1074-7613(00)00062-5

PMID:11114375

Abstract

We have identified the lymphocyte semaphorin CD100/Sema4D as a CD40-inducible molecule by subtractive cDNA cloning. CD100 stimulation significantly enhanced the effects of CD40 on B cell responses. Administration of soluble CD100 markedly accelerated in vivo antigen-specific antibody responses. CD100 receptors with different binding affinities were detected on renal tubular cells (K(d) = approximately 1 x 10(-9)M) and lymphocytes (K(d) = approximately 3 x 10(-7)M). Expression cloning revealed that the CD100 receptor on lymphocytes is CD72, a negative regulator of B cell responsiveness. CD72 thus represents a novel class of semaphorin receptors. CD100 stimulation induced tyrosine dephosphorylation of CD72 and dissociation of SHP-1 from CD72. Our findings indicate that CD100 plays a critical role in immune responses by the novel mechanism of turning off negative signaling by CD72.

摘要

我们通过消减cDNA克隆鉴定出淋巴细胞信号素CD100/Sema4D是一种CD40诱导分子。CD100刺激显著增强了CD40对B细胞反应的作用。给予可溶性CD100可显著加速体内抗原特异性抗体反应。在肾小管细胞（解离常数K(d)约为1×10(-9)M）和淋巴细胞（K(d)约为3×10(-7)M）上检测到具有不同结合亲和力的CD100受体。表达克隆显示淋巴细胞上的CD100受体是CD72，它是B细胞反应性的负调节因子。因此，CD72代表了一类新型的信号素受体。CD100刺激诱导CD72的酪氨酸去磷酸化以及SHP-1从CD72上解离。我们的研究结果表明，CD100通过关闭CD72的负信号这一新型机制在免疫反应中发挥关键作用。