Radhakrishnan Suresh, Nguyen Loc T, Ciric Bogoljub, Ure Daren R, Zhou Bin, Tamada Koji, Dong Haidong, Tseng Su-Yi, Shin Tahiro, Pardoll Drew M, Chen Lieping, Kyle Robert A, Rodriguez Moses, Pease Larry R
Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
J Immunol. 2003 Feb 15;170(4):1830-8. doi: 10.4049/jimmunol.170.4.1830.
A human IgM Ab, serum-derived human IgM 12 (sHIgM12), is identified that binds mouse and human dendritic cells (DC), inducing dramatic immunopotentiation following treatment of the mouse DC in vitro. Competition, transfection, and knockout studies identified the ligand on mouse DC as the costimulatory molecule family member B7-DC. Potent T cell responses are stimulated by Ag-pulsed DC treated with the sHIgM12 Ab in vitro and upon adoptive transfer of Ab-treated Ag-pulsed DC into animals. The multivalent structure of pentameric IgM provides the potential for cross-linking cell surface targets, endowing the soluble Abs with biological potential not normally associated with immune function. The ability of the sHIgM12 Ab to potentiate the immune response is dependent on the multimeric structure of IgM, as bivalent monomers do not retain this property. Furthermore, pretreatment of DC with IgM monomers blocks subsequent potentiation by intact IgM pentamers, an indication that cross-linking of B7-DC on the cell surface is critical for potentiation of Ag presentation. These findings imply that, in addition to known costimulatory roles, B7-DC can function as a receptor for signals delivered by cells expressing B7-DC ligands.
一种人源IgM抗体，即血清来源的人IgM 12（sHIgM12），被鉴定出可结合小鼠和人的树突状细胞（DC），在体外处理小鼠DC后可诱导显著的免疫增强作用。竞争性、转染和基因敲除研究确定小鼠DC上的配体为共刺激分子家族成员B7-DC。用sHIgM12抗体体外处理经抗原脉冲刺激的DC，以及将经抗体处理的抗原脉冲刺激的DC过继转移到动物体内后，均可刺激强烈的T细胞反应。五聚体IgM的多价结构提供了交联细胞表面靶点的潜力，赋予了可溶性抗体通常与免疫功能无关的生物学潜能。sHIgM12抗体增强免疫反应的能力取决于IgM的多聚体结构，因为二价单体不具备这种特性。此外，用IgM单体预处理DC可阻断随后完整IgM五聚体的增强作用，这表明细胞表面B7-DC的交联对于增强抗原呈递至关重要。这些发现意味着，除了已知的共刺激作用外，B7-DC还可作为表达B7-DC配体的细胞传递信号的受体发挥作用。
