Prechl József
R&D Laboratory, Diagnostcum zrt, Budapest, Hungary.
Clin Transl Immunology. 2017 Nov 17;6(11):e161. doi: 10.1038/cti.2017.50. eCollection 2017 Nov.
The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]=. This zone corresponds to the biologically relevant range of reversible interactions. We show that thermodynamic and kinetic properties of antibody-antigen interactions correlate with immunological functions. The formation of stable, long-lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher-order complexes. As the energy of formation of complexes increases, we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation-related immune effector processes, linking the physicochemical principles of innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a wide range of affinities, allowing the continuous sampling of antibody-bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by crosslinking these receptors on effector cells with increasing enzymatic degradation potential. Thus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a quantitative adaptive immune system, which regulates molecular integrity of the host by tuning the degradation and recycling of molecules from silent removal to inflammatory elimination.
抗体的稳态可被描述为一个由相互作用网络调节的平衡生产、靶标结合和受体介导的消除过程，该网络控制着B细胞的发育和选择。最近，我们提出了一个定量模型来描述相互作用伙伴的浓度和亲和力如何产生一个网络。在此，我们认为这种物理定量方法可扩展用于解释抗体的效应功能。我们将全局抗体平衡定义为游离抗体、游离抗原和免疫复合物浓度以及表观亲和力解离常数的摩尔当量区域：[Ab]=[Ag]=[AbAg]= 。该区域对应于生物学相关的可逆相互作用范围。我们表明抗体 - 抗原相互作用的热力学和动力学性质与免疫功能相关。稳定、长寿免疫复合物的形成对应于熵的降低，并且是高阶复合物产生的先决条件。随着复合物形成能量的增加，我们观察到从沉默清除到炎症反应的逐渐转变。这些规则也可应用于补体激活相关的免疫效应过程，将先天性和适应性体液反应的物理化学原理联系起来。介导效应功能的受体亲和力显示出广泛的范围，允许在整个浓度范围内持续采样抗体结合的抗原。多价、多组分复合物的产生通过交联效应细胞上具有增加酶促降解潜力的这些受体来触发效应功能。因此，抗体稳态是一个具有复杂网络特性的热力学系统，通过适当的免疫调节和效应途径嵌套在宿主生物体中。全局抗体平衡的维持是通过先天定性信号调节定量适应性免疫系统来实现的，该系统通过调整分子从沉默清除到炎症消除的降解和再循环来调节宿主的分子完整性。
