Mohr Marcel, Hose Dirk, Seckinger Anja, Marciniak-Czochra Anna
Heidelberg University, Institute of Applied Mathematics, BIOQUANT and IWR, Heidelberg, Germany.
Heidelberg University Hospital, Medical Clinic V, Heidelberg, Germany.
R Soc Open Sci. 2018 Jan 24;5(1):170759. doi: 10.1098/rsos.170759. eCollection 2018 Jan.
Plasma cells (PCs) are the main antibody-producing cells in humans. They are long-lived so that specific antibodies against either pathogens or vaccines are produced for decades. PC longevity is attributed to specific areas within the bone marrow micro-environment, the so-called 'niche', providing the cells with required growth and survival factors. With antigen encounters, e.g. infection or vaccination, new PCs are generated and home to the bone marrow where they compete with resident PCs for the niche. We propose a parametrized mathematical model describing healthy PC dynamics in the bone marrow. The model accounts for competition for the niche between newly produced PCs owing to vaccination and resident PCs. Mathematical analysis and numerical simulations of the model allow explanation of the recovery of PC homoeostasis after a vaccine-induced perturbation, and the fraction of vaccine-specific PCs inside the niche. The model enables quantification of the niche-related dynamics of PCs, i.e. the duration of PC transition into the niche and the impact of different rates for PC transitions into and out of the niche on the observed cell dynamics. Ultimately, it provides a potential basis for further investigations in health and disease.
浆细胞（PCs）是人类主要的抗体产生细胞。它们寿命很长，因此针对病原体或疫苗的特异性抗体能够产生数十年。PC的长寿归因于骨髓微环境中的特定区域，即所谓的“生态位”，该区域为细胞提供所需的生长和存活因子。遇到抗原时，例如感染或接种疫苗，新的PC会产生并归巢至骨髓，在那里它们与驻留的PC竞争生态位。我们提出了一个参数化数学模型，用于描述骨髓中健康PC的动态变化。该模型考虑了由于接种疫苗产生的新PC与驻留PC之间对生态位的竞争。对该模型进行数学分析和数值模拟，可以解释疫苗诱导的扰动后PC稳态的恢复情况，以及生态位内疫苗特异性PC的比例。该模型能够量化PC与生态位相关的动态变化，即PC过渡到生态位的持续时间，以及不同的PC进入和离开生态位的速率对观察到的细胞动态变化的影响。最终，它为健康和疾病的进一步研究提供了潜在基础。
