Iber Dagmar, Maini Philip K
Centre for Mathematical Biology, Mathematical Institute, 24-29 St Giles, Oxford OX1 3LB, UK.
J Theor Biol. 2002 Nov 21;219(2):153-75. doi: 10.1006/jtbi.2002.3079.
We present a mathematical model which reproduces experimental data on the germinal centre (GC) kinetics of the primed primary immune response and on affinity maturation observed during the reaction. We show that antigen masking by antibodies which are produced by emerging plasma cells can drive affinity maturation and provide a feedback mechanism by which the reaction is stable against variations in the initial antigen amount over several orders of magnitude. This provides a possible answer to the long-standing question of the role of antigen reduction in driving affinity maturation. By comparing model predictions with experimental results, we propose that the selection probability of centrocytes and the recycling probability of selected centrocytes are not constant but vary during the GC reaction with respect to time. It is shown that the efficiency of affinity maturation is highest if clones with an affinity for the antigen well above the average affinity in the GC leave the GC for either the memory or plasma cell pool. It is further shown that termination of somatic hypermutation several days before the end of the germinal centre reaction is beneficial for affinity maturation. The impact on affinity maturation of simultaneous initiation of memory cell formation and somatic hypermutation vs. delayed initiation of memory cell formation is discussed.
我们提出了一个数学模型，该模型再现了关于初次致敏初级免疫反应生发中心（GC）动力学以及反应过程中观察到的亲和力成熟的实验数据。我们表明，新生浆细胞产生的抗体对抗原的掩盖可驱动亲和力成熟，并提供一种反馈机制，通过该机制反应对于初始抗原量在几个数量级上的变化具有稳定性。这为长期存在的抗原减少在驱动亲和力成熟中所起作用的问题提供了一个可能的答案。通过将模型预测结果与实验结果进行比较，我们提出中心细胞的选择概率和选定中心细胞的循环概率并非恒定不变，而是在GC反应过程中随时间变化。结果表明，如果对抗原的亲和力远高于GC中平均亲和力的克隆离开GC进入记忆或浆细胞库，亲和力成熟的效率最高。进一步表明，在生发中心反应结束前几天终止体细胞高频突变有利于亲和力成熟。讨论了记忆细胞形成和体细胞高频突变同时启动与记忆细胞形成延迟启动对亲和力成熟的影响。
