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抗体动力学模拟——克隆缺失和体细胞超突变的数学探索

Antibody Dynamics Simulation-A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation.

作者信息

Xu Zhaobin, Peng Qingzhi, Liu Weidong, Demongeot Jacques, Wei Dongqing

机构信息

Department of Life Science, Dezhou University, Dezhou 253023, China.

Department of Physical Education, Dezhou University, Dezhou 253023, China.

出版信息

Biomedicines. 2023 Jul 20;11(7):2048. doi: 10.3390/biomedicines11072048.

Abstract

We have employed mathematical modeling techniques to construct a comprehensive framework for elucidating the intricate response mechanisms of the immune system, facilitating a deeper understanding of B-cell clonal deletion and somatic hypermutation. Our improved model introduces innovative mechanisms that shed light on positive and negative selection processes during T-cell and B-cell development. Notably, clonal deletion is attributed to the attenuated immune stimulation exerted by self-antigens with high binding affinities, rendering them less effective in eliciting subsequent B-cell maturation and differentiation. Secondly, our refined model places particular emphasis on the crucial role played by somatic hypermutation in modulating the immune system's functionality. Through extensive investigation, we have determined that somatic hypermutation not only expedites the production of highly specific antibodies pivotal in combating microbial infections but also serves as a regulatory mechanism to dampen autoimmunity and enhance self-tolerance within the organism. Lastly, our model advances the understanding of the implications of antibody in vivo evolution in the overall process of organismal aging. With the progression of time, the age-associated amplification of autoimmune activity becomes apparent. While somatic hypermutation effectively delays this process, mitigating the levels of autoimmune response, it falls short of reversing this trajectory entirely. In conclusion, our advanced mathematical model offers a comprehensive and scholarly approach to comprehend the intricacies of the immune system. By encompassing novel mechanisms for selection, emphasizing the functional role of somatic hypermutation, and illuminating the consequences of in vivo antibody evolution, our model expands the current understanding of immune responses and their implications in aging.

摘要

我们运用数学建模技术构建了一个全面的框架,以阐明免疫系统复杂的反应机制,促进对B细胞克隆清除和体细胞高频突变的深入理解。我们改进后的模型引入了创新机制,揭示了T细胞和B细胞发育过程中的阳性和阴性选择过程。值得注意的是,克隆清除归因于具有高结合亲和力的自身抗原所施加的减弱的免疫刺激,使其在引发后续B细胞成熟和分化方面效果较差。其次,我们改进后的模型特别强调了体细胞高频突变在调节免疫系统功能中所起的关键作用。通过广泛研究,我们确定体细胞高频突变不仅加速了对抗微生物感染至关重要的高特异性抗体的产生,而且还作为一种调节机制来抑制自身免疫并增强机体的自我耐受性。最后,我们的模型推进了对抗体在体内进化在机体衰老整个过程中的影响的理解。随着时间的推移,与年龄相关的自身免疫活性增强变得明显。虽然体细胞高频突变有效地延迟了这一过程,减轻了自身免疫反应的水平,但它并不能完全扭转这一轨迹。总之,我们先进的数学模型提供了一种全面且学术性的方法来理解免疫系统的复杂性。通过纳入新颖的选择机制、强调体细胞高频突变的功能作用以及阐明体内抗体进化的后果,我们的模型扩展了当前对免疫反应及其在衰老中的影响的理解。

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