英国帝国理工学院Omer Karin研究组的一项最新研究，探明了竞争对浆细胞寿命的调节解释了抗体持久性的寿命和异质性。该研究于2024年3月5日发表于国际一流学术期刊《免疫》杂志上。

研究团队利用一个数学框架来探索浆细胞清除的动态及其受存活因子调控的机制。对甲型肝炎和乙型肝炎以及HPV疫苗接种后抗体持久性的分析，揭示了应答内部和应答之间的特异性寿命模式和异质性，这意味着这一过程在两种动态机制之间的临界“平坦”状态附近进行了微调。

这种临界状态反映了潜在调节网络的速率调整，并且对参数的变化高度敏感，这增强了细胞之间的寿命差异。课题组人员认为微调是共享生存信号竞争的一般结果，基于竞争的机制提供了一种统一的解释，涵盖了广泛的实验观察，包括浆细胞积累的动力学和生存因子缺失的影响。他们的理论是可检验的，研究人员提供具体的预测。

据了解，在感染或接种疫苗后出现的浆细胞展现出不同的寿命，大多数存活数天到数月，而另一些则持续数十年，提供特异性抗原的长期保护。

附：英文原文

Title: Tuning of plasma cell lifespan by competition explains the longevity and heterogeneity of antibody persistence

Author: Benjamin D. Simons, Omer Karin

Issue&Volume: 2024-03-05

Abstract: Plasma cells that emerge after infection or vaccination exhibit heterogeneous lifespans; most survive for days to months, whereas others persist for decades, providing antigen-specific long-term protection. We developed a mathematical framework to explore the dynamics of plasma cell removal and its regulation by survival factors. Analyses of antibody persistence following hepatitis A and B and HPV vaccination revealed specific patterns of longevity and heterogeneity within and between responses, implying that this process is fine-tuned near a critical “flat” state between two dynamic regimes. This critical state reflects the tuning of rates of the underlying regulatory network and is highly sensitive to variation in parameters, which amplifies lifespan differences between cells. We propose that fine-tuning is the generic outcome of competition over shared survival signals, with a competition-based mechanism providing a unifying explanation for a wide range of experimental observations, including the dynamics of plasma cell accumulation and the effects of survival factor deletion. Our theory is testable, and we provide specific predictions.

DOI: 10.1016/j.immuni.2024.02.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00081-5