Marzocchi-Machado C M, Polizello A C, Azzolini A E, Lucisano-Valim Y M
Department of Parasitology, Microbiology and Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Immunol Invest. 1999 Mar-May;28(2-3):89-101. doi: 10.3109/08820139909061139.
A systematic study was carried out to investigate the role of antibody functional affinity in the capacity of immune complexes (IC) to activate the complement system and to trigger subsequently the molecular events involved in the handling of IC by providing a clearance mechanism. For this purpose, two populations of polyclonal anti-BSA IgG antibodies of different affinities were prepared, with values of 1.89x10(8) M(-1) and 4.94x10(8) M(-1). First we studied the capacity of IC formed at equivalence with both antibodies to activate the classical and the alternative pathways of human complement and the ability of the complexes to bind to erythrocyte C3b-C4b receptors (CR1; CD35). The data showed that the highest affinity antibodies were more efficient in activating complement by both pathways. However, their binding to erythrocyte CR1 was significantly lower compared to the binding of the lowest affinity IgG. Second we compared these IC in terms of their ability to stimulate the respiratory burst of neutrophils (PMN) and to induce the release of PMN lysosomal enzymes. In general, both of these PMN functions were better stimulated by the IC prepared with the IgG antibodies having a highest affinity, although the effects were variable for different IC concentrations. The suggestion to be drawn from the data is that the antibody affinity has an influence on the formation of the immune complex lattice, modulating its three-dimensional structure and the arrangement of the antibody Fc fragments, interfering with complement activation and access to the neutrophil IgG receptors. The significance of these observations for the understanding of how affinity influences the precise biological mechanism that participates in the fate of IC is discussed.
开展了一项系统性研究，以探讨抗体功能亲和力在免疫复合物（IC）激活补体系统的能力中所起的作用，并通过提供一种清除机制，随后触发参与IC处理的分子事件。为此，制备了两群亲和力不同的多克隆抗牛血清白蛋白IgG抗体，其亲和力值分别为1.89×10⁸ M⁻¹和4.94×10⁸ M⁻¹。首先，我们研究了与这两种抗体在等价条件下形成的IC激活人补体经典途径和替代途径的能力，以及这些复合物与红细胞C3b - C4b受体（CR1；CD35）结合的能力。数据表明，高亲和力抗体通过这两种途径激活补体的效率更高。然而，与最低亲和力IgG的结合相比，它们与红细胞CR1的结合显著降低。其次，我们比较了这些IC在刺激中性粒细胞（PMN）呼吸爆发和诱导PMN溶酶体酶释放方面的能力。总体而言，由具有最高亲和力的IgG抗体制备的IC对这两种PMN功能的刺激效果更好，尽管不同IC浓度下的效果存在差异。从数据中得出的结论是，抗体亲和力对免疫复合物晶格的形成有影响，调节其三维结构和抗体Fc片段的排列，干扰补体激活以及与中性粒细胞IgG受体的结合。讨论了这些观察结果对于理解亲和力如何影响参与IC命运的精确生物学机制的意义。
