In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this first paper, we describe the cycles of B-cell expansion and differentiation driven by B-cell receptor engagement. The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. We express BCR engagement as a function of apparent affinity and free antigen concentration, using the range of 10-14-10-3 M for both factors. We assume that for keeping their BCR responsive, B cells must maintain partial BCR saturation, which is a narrow region defined by [Ag]≈KD. To remain in this region, B cells respond to changes in [Ag] by proliferation or apoptosis and modulate KD by changing BCR structure. We apply this framework to various niches of B-cell development such as the bone marrow, blood, lymphoid follicles and germinal centers. We propose that clustered B cells in the bone marrow and in follicles present antigen to surrounding B cells by exposing antigen captured on complement and Fc receptors. The model suggests that antigen-dependent selection in the bone marrow results in (1) effector BI cells, which develop in blood as a consequence of the inexhaustible nature of soluble antigens, (2) memory cells that survive in antigen rich niches, identified as marginal zone B cells. Finally, the model implies that memory B cells could derive survival signals from abundant non-cognate antigens.

中文翻译：

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通用的定量抗体稳态模型：通过BCR饱和和对骨髓功能的新见解来调节B细胞发育。

在一对文章中，我们提出了克隆体液免疫系统的稳态功能的通用量化模型。在第一篇论文中，我们描述了由B细胞受体参与驱动的B细胞扩增和分化周期。B细胞的命运取决于其在生命的任何时刻通过其抗原受体接收到的信号。我们将BCR参与表达为表观亲和力和游离抗原浓度的函数，两个因素均使用10-14-10-3 M的范围。我们假设为了保持其BCR响应，B细胞必须保持部分BCR饱和，这是由[Ag]≈KD定义的狭窄区域。为了保留在该区域，B细胞通过增殖或凋亡来响应[Ag]的变化，并通过改变BCR结构来调节KD。我们将此框架应用于B细胞发育的各个领域，例如骨髓，血液，淋巴滤泡和生发中心。我们建议通过暴露捕获在补体和Fc受体上的抗原，将骨髓和卵泡中的簇状B细胞呈现给周围的B细胞抗原。该模型表明，骨髓中抗原依赖的选择会导致（1）效应BI细胞，其由于可溶性抗原的不竭消耗而在血液中发育；（2）在富含抗原的壁ches中存活的记忆细胞，被鉴定为边缘区B细胞。最后，该模型暗示记忆B细胞可以从丰富的非同源抗原中获得生存信号。我们建议通过暴露补体和Fc受体捕获的抗原，将骨髓和卵泡中的簇状B细胞呈现给周围的B细胞抗原。该模型表明，骨髓中抗原依赖的选择会导致（1）效应BI细胞，其由于可溶性抗原的不竭消耗而在血液中发育；（2）在富含抗原的壁ches中存活的记忆细胞，被鉴定为边缘区B细胞。最后，该模型暗示记忆B细胞可以从丰富的非同源抗原中获得生存信号。我们建议通过暴露补体和Fc受体捕获的抗原，将骨髓和卵泡中的簇状B细胞呈现给周围的B细胞抗原。该模型表明，骨髓中抗原依赖的选择会导致（1）效应BI细胞，其由于可溶性抗原的不竭消耗而在血液中发育；（2）在富含抗原的壁ches中存活的记忆细胞，被鉴定为边缘区B细胞。最后，该模型暗示记忆B细胞可以从丰富的非同源抗原中获得生存信号。（2）在抗原丰富的壁ni中存活的记忆细胞，被鉴定为边缘区B细胞。最后，该模型暗示记忆B细胞可以从丰富的非同源抗原中获得生存信号。（2）在抗原丰富的壁ni中存活的记忆细胞，被鉴定为边缘区B细胞。最后，该模型暗示记忆B细胞可以从丰富的非同源抗原中获得生存信号。