Hirano Testuo, Yonekubo Isao, Shimo Kuniaki, Mizuguchi Junichiro
Department of Immunology and Intractable Disease Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, 160-8402, Tokyo, Japan.
Immunol Lett. 2003 Oct 31;89(2-3):251-7. doi: 10.1016/s0165-2478(03)00156-1.
CD40, a member of the tumor necrosis factor receptor (TNFR) family, promotes IgM, IgG, and IgA antibody (Ab) synthesis in combination with a variety of cytokines. Another TNFR family member, CD27, causes B cells to differentiate into antibody-forming cells, with marginal effects on proliferation. In the present study, we examined whether anti-CD27 monoclonal antibody (mAb) modulates the antibody production induced by anti-CD40 mAb immobilized on L cells expressing FcgammaRII (CDw32) in the presence of IL-2 and/or IL-10. The anti-CD40 mAb substantially enhanced IgM, IgG, and IgA production in combination with IL-2 and IL-10, whereas anti-CD27 mAb augmented it only marginally, as assessed by enzyme-linked immunosorbent assay. The addition of anti-CD27 mAb enhanced the anti-CD40-mediated IgM, IgG, and IgA antibody production only when both IL-2 and IL-10 were present in the culture. The CD27-positive B cell compartment generated synergistic antibody responses in response to four different stimulants, anti-CD27/anti-CD40 mAb and cytokines IL-2/IL-10, whereas the CD27-negative B cell compartment failed to do so. Kinetic analysis showed that anti-CD40 might function in the early phase of B cell activation, while anti-CD27 mAb functioned in the late stage. The addition of CD27(-) to CD27(+) B cells in various ratios did not have any effect on the antibody production, suggesting that CD27(+) to CD27(-) B cell interaction does not occur in this system. Our findings suggest that a member of the TNFR family, CD27, cooperates with CD40 to induce efficient antibody production in combination with cytokines IL-2 and IL-10.
CD40是肿瘤坏死因子受体（TNFR）家族的一员，与多种细胞因子共同作用可促进IgM、IgG和IgA抗体（Ab）的合成。TNFR家族的另一个成员CD27可使B细胞分化为抗体形成细胞，对增殖的影响较小。在本研究中，我们检测了抗CD27单克隆抗体（mAb）是否能在白细胞介素-2（IL-2）和/或白细胞介素-10存在的情况下，调节固定在表达FcγRII（CDw32）的L细胞上的抗CD40 mAb诱导的抗体产生。通过酶联免疫吸附测定法评估，抗CD40 mAb与IL-2和IL-10共同作用时可显著增强IgM、IgG和IgA的产生，而抗CD27 mAb的增强作用仅很微弱。仅当培养物中同时存在IL-2和IL-10时，添加抗CD27 mAb才会增强抗CD40介导的IgM、IgG和IgA抗体产生。CD27阳性B细胞亚群对四种不同刺激物（抗CD27/抗CD40 mAb和细胞因子IL-2/IL-10）产生协同抗体反应，而CD27阴性B细胞亚群则不能。动力学分析表明，抗CD40可能在B细胞活化的早期起作用，而抗CD27 mAb在后期起作用。以不同比例将CD27（-）B细胞添加到CD27（+）B细胞中对抗体产生没有任何影响，这表明在该系统中不存在CD27（+）与CD27（-）B细胞之间的相互作用。我们的研究结果表明，TNFR家族的成员CD27与CD40协同作用，在细胞因子IL-2和IL-10的共同作用下诱导高效的抗体产生。
