B淋巴细胞生成中反馈信号的动力学特性：一种数学建模方法
Dynamical properties of feedback signalling in B lymphopoiesis: A mathematical modelling approach
摘要：
造血是血细胞生成的过程。造血产生淋巴细胞，负责适应性免疫反应的细胞。这一过程的中断与白血病等疾病有关，这在儿童中尤其常见。这一过程的自我调节特性使它们适合于数学研究。在本文中，我们开发的数学模型的淋巴细胞生成使用目前可用的数据。我们从现有的细胞谱系发育结构模型中汲取灵感，并将其与儿科骨髓数据相结合，特别关注调控机制。对模型进行了形式化的分析，给出了稳态及其稳定性条件。我们使用这种分析来获得参数空间的生物相关区域，并了解B细胞更新的动力学行为。最后，我们使用数值模拟，以获得进一步了解的增殖和成熟率的影响，在B线的细胞重建。我们的结论是，一个模型，包括反馈调节细胞增殖代表了一个生物学上合理的描述B细胞重建骨髓。对B淋巴细胞生成的精确动力学描述有助于血液系统疾病的研究。
英文摘要：
Haematopoiesis is the process of generation of blood cells. Lymphopoiesis generates lymphocytes, the cells in charge of the adaptive immune response. Disruptions of this process are associated with diseases like leukaemia, which is especially incident in children. The characteristics of self-regulation of this process make them suitable for a mathematical study. In this paper we develop mathematical models of lymphopoiesis using currently available data. We do this by drawing inspiration from existing structured models of cell lineage development and integrating them with paediatric bone marrow data, with special focus on regulatory mechanisms. A formal analysis of the models is carried out, giving steady states and their stability conditions. We use this analysis to obtain biologically relevant regions of the parameter space and to understand the dynamical behaviour of B-cell renovation. Finally, we use numerical simulations to obtain further insight into the influence of proliferation and maturation rates on the reconstitution of the cells in the B line. We conclude that a model including feedback regulation of cell proliferation represents a biologically plausible depiction for B-cell reconstitution in bone marrow. Research into haematological disorders could benefit from a precise dynamical description of B lymphopoiesis.
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