Immunons revisited: Binding of multivalent antigens to B cells
Immunons revisited: Binding of multivalent antigens to B cells
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DOI：
10.1016/s0161-5890(96)00096-x
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发表时间：
1997-01-01
影响因子：
3.6
通讯作者：
Perelson, AS
中科院分区：
文献类型：
--
作者：
Sulzer, B;Perelson, AS
高度多价半抗原-聚合物制剂诱导的T非依赖性B细胞应答已被广泛研究。体外测量的剂量-反应曲线大致呈钟形，峰值反应发生在非常低的配体浓度下，对于各种不同的配体，在0.1-1 ng/ml之间。此外。具有超过约10个半抗原的聚合物倾向于刺激，而具有少于10个半抗原缀合的聚合物倾向于抑制。这些观察结果一直令人困惑的背景下，被视为受体连接的多价配体的标准理论。我们提出了一个新的分析，这些以前的实验，调和理论和实验之间的差异。从该理论可以得出结论，所观察到的剂量-反应曲线中的峰仅微弱地反映了配体的性质和表面免疫球蛋白对半抗原的亲和力，但强烈地依赖于培养物中抗原特异性B细胞的密度。在低配体浓度下，响应细胞的数量减少，因为细胞必须共享有限量的配体，而不是因为受体和配体彼此相遇的概率降低。我们的理论得出了与先前研究人员相同的结论，即为了刺激B细胞，需要将最少数量的受体位点（数量级为10）结合到单个配体上。虽然这一结论是基于携带少于最低数量的半抗原的抗原缺乏免疫原性，但本研究的定量结果（来自用高度多价抗原获得的拟合实验剂量-反应曲线）为免疫子假说提供了证据基于受体聚集程度。我们的理论还提供了定量的协议与系统的实验观察，其中刺激和非刺激聚合物混合在同一系统中。(C)1997 Elsevier Science Ltd.
The T-independent B cell response induced by highly multivalent hapten-polymer preparations has been studied extensively. The in vitro measured dose-response curve lends to be roughly bell-shaped with the peak response occurring at very low ligand concentrations, between 0.1-1 ng/ml for a variety of different ligands. Furthermore. polymers with more than approximately 10 haptens tend to be stimulatory, whereas polymers with fewer than 10 haptens conjugated, tend to be inhibitory. These observations have been perplexing when viewed within the context of standard theories of receptor ligation by multivalent ligands. We present a new analysis of these previous experiments that reconciles the differences between theory and experiment. From this theory it is concluded that the peak in the observed dose-response curve only weakly reflects properties of the ligand and the affinity of surface immunoglobulin for the hapten, but depends strongly on the density of antigen-specific B cells in the culture. The number of responding cells decreases at low ligand concentrations, because cells have to share limiting amounts of ligand and not because of the decreasing probability of receptors and ligands meeting each other. Our theory leads to the same conclusion as made by previous researchers, namely that a minimum number of receptor sites, of the order of 10, need to be bound to a single ligand in order to stimulate a B cell. While this conclusion was based on the lack of immunogenicity of antigens carrying less than a minimum number of haptens, the quantitative results of this study, derived from fitting experimental dose-response curves obtained with highly multivalent antigens, provide evidence for the immunon hypothesis that is based upon the degree of receptor aggregation. Our theory also provides quantitative agreement with experimental observations on systems, in which both stimulatory and non-stimulatory polymers are mixed in the same system. (C) 1997 Elsevier Science Ltd.