斑马鱼B细胞VDJ利用相关性的多尺度模型
A Multi-Scale Model for Correlation in B Cell VDJ Usage of Zebrafish
摘要：
斑马鱼（\emph{Danio rerio}）是免疫学研究的模式动物之一，其适应性免疫系统的动态与高等动物相似。在这项工作中，我们建立了一个多尺度模型来模拟B细胞在斑马鱼的初级和次级免疫反应中的动力学。我们用这个模型来解释的VDJ使用B细胞库在个别斑马鱼之间的相关性。我们使用延迟常微分方程（ODE）系统来模拟斑马鱼在6个月寿命内的免疫反应。该平均场理论给出了感染期间高亲和力B细胞的数量作为时间的函数。然后，这些B细胞的序列取自通过“微观”随机能量模型计算的分布。这种广义的$NK$模型表明，对一种抗原特异的成熟B细胞主要具有单一VDJ重组。该模型允许第一原理计算的概率，$p$，两个斑马鱼响应相同的抗原将选择相同的VDJ重组。该概率$p$随着B细胞群体大小和B细胞选择强度而增加。概率$p$随着B细胞超突变率而降低。多尺度模型预测的斑马鱼免疫系统的相关性与实验结果高度相似。
英文摘要：
The zebrafish (\emph{Danio rerio}) is one of the model animals for study of immunology because the dynamics in the adaptive immune system of zebrafish are similar to that in higher animals. In this work, we built a multi-scale model to simulate the dynamics of B cells in the primary and secondary immune responses of zebrafish. We use this model to explain the reported correlation between VDJ usage of B cell repertoires in individual zebrafish. We use a delay ordinary differential equation (ODE) system to model the immune responses in the 6-month lifespan of a zebrafish. This mean field theory gives the number of high affinity B cells as a function of time during an infection. The sequences of those B cells are then taken from a distribution calculated by a "microscopic" random energy model. This generalized $NK$ model shows that mature B cells specific to one antigen largely possess a single VDJ recombination. The model allows first-principles calculation of the probability, $p$, that two zebrafish responding to the same antigen will select the same VDJ recombination. This probability $p$ increases with the B cell population size and the B cell selection intensity. The probability $p$ decreases with the B cell hypermutation rate. The multi-scale model predicts correlations in the immune system of the zebrafish that are highly similar to that from experiment.
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