Data_Sheet_1_Synchronous Germinal Center Onset Impacts the Efficiency of Antibody Responses.pdf

The germinal center reaction is an important target for modulating antibody responses. Antibody production from germinal centers is regulated by a negative feedback mechanism termed antibody feedback. By imposing antibody feedback, germinal centers can interact and regulate the output of other germinal centers. Using an agent-based model of the germinal center reaction, we studied the impact of antibody feedback on kinetics and efficiency of a germinal center. Our simulations predict that high feedback of antibodies from germinal centers reduces the production of plasma cells and subsequently the efficiency of the germinal center reaction by promoting earlier termination. Affinity maturation is only weakly improved by increased antibody feedback and ultimately interrupted because of premature termination of the reaction. The model predicts that the asynchronous onset and changes in number of germinal centers could alter the efficiency of antibody response due to changes in feedback by soluble antibodies. Consequently, late initialized germinal centers have a compromised output due to higher antibody feedback from the germinal centers formed earlier. The results demonstrate potential effects of germinal center intercommunication and highlight the importance of understanding germinal center interactions for optimizing the antibody response, in particular, in the elderly and in the context of vaccination.

生发中心反应是调节抗体反应的关键靶点。生发中心产生的抗体通过称为抗体反馈的负反馈机制进行调节。通过施加抗体反馈，生发中心能够相互交互并调节其他生发中心的功能输出。利用生发中心反应的基于智能体模型，我们研究了抗体反馈对生发中心动力学和效率的影响。我们的模拟预测，生发中心产生的高水平抗体反馈会减少浆细胞的生成，进而通过促进早期终止来降低生发中心反应的效率。亲和力成熟仅因抗体反馈的增加而得到微弱改善，并最终因反应的提前终止而被中断。模型预测，生发中心的不同步出现和数量的变化可能会由于可溶性抗体的反馈变化而改变抗体反应的效率。因此，由于早期形成的生发中心产生更高的抗体反馈，晚启动的生发中心输出受损。这些结果展示了生发中心间通讯的潜在影响，并突出了理解生发中心相互作用对于优化抗体反应的重要性，尤其是在老年人和疫苗接种的背景下。