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
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita Osaka 565-0871, Japan.
Immunity. 2000 Nov;13(5):621-31. doi: 10.1016/s1074-7613(00)00062-5.
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.
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。
