Immunology Division, Walter and Eliza Hall Institute for Medical Research, Australia.
J Theor Biol. 2010 May 21;264(2):443-9. doi: 10.1016/j.jtbi.2010.02.019. Epub 2010 Feb 19.
Recent studies of the population dynamics of a system of lymphocytes in an in vitro immune response have reported strong correlations in cell division times, both between parents and their progeny, and between those of sibling cells. The data also show a high level of correlation in the ultimate number of divisions achieved by cells within the same clone. Such correlations are often ignored in mathematical models of cell dynamics as they violate a standard assumption in the theory of branching processes, that of the statistical independence of cells. In this article we present a model in which these correlations can be incorporated, and have used this model to study the effect of these correlations on the population dynamics of a system of cells. We found that correlation in the division times between parents and their progeny can alter the mean population size of clones within the system, while all of the correlations can affect the variance in the sizes of different clones. The model was then applied to experimental data obtained from time-lapse video microscopy of a system of CpG stimulated B lymphocytes and it was found that inclusion of the correct correlation structure is necessary to accurately reproduce the observed population dynamics. We conclude that correlations in the dynamics of cells within an ensemble will affect the population dynamics of the system, and the effects will become more pronounced as the number of divisions increases.
最近对体外免疫反应中淋巴细胞系统的种群动态的研究报告表明，细胞分裂时间之间存在强烈的相关性，无论是父母与其后代之间，还是兄弟姐妹细胞之间。这些数据还显示，同一克隆内细胞达到的最终分裂次数也存在高度相关性。在细胞动力学的数学模型中，通常会忽略这些相关性，因为它们违反了分支过程理论中的一个标准假设，即细胞的统计独立性。在本文中，我们提出了一个可以包含这些相关性的模型，并使用该模型研究了这些相关性对细胞系统种群动态的影响。我们发现，父母与其后代之间的分裂时间的相关性可以改变系统内克隆的平均种群大小，而所有的相关性都可以影响不同克隆大小的方差。然后，该模型被应用于从 CpG 刺激的 B 淋巴细胞的延时视频显微镜获得的实验数据，结果发现，包含正确的相关结构对于准确再现观察到的种群动态是必要的。我们得出结论，在一个集合中细胞的动力学相关性将影响系统的种群动态，并且随着分裂次数的增加，影响将变得更加显著。
