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

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 mechanism...

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Autores principales: Xu, Zhaobin, Peng, Qingzhi, Liu, Weidong, Demongeot, Jacques, Wei, Dongqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377040/
https://www.ncbi.nlm.nih.gov/pubmed/37509687
http://dx.doi.org/10.3390/biomedicines11072048
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author Xu, Zhaobin
Peng, Qingzhi
Liu, Weidong
Demongeot, Jacques
Wei, Dongqing
author_facet Xu, Zhaobin
Peng, Qingzhi
Liu, Weidong
Demongeot, Jacques
Wei, Dongqing
author_sort Xu, Zhaobin
collection PubMed
description 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.
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spelling pubmed-103770402023-07-29 Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation Xu, Zhaobin Peng, Qingzhi Liu, Weidong Demongeot, Jacques Wei, Dongqing Biomedicines Article 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. MDPI 2023-07-20 /pmc/articles/PMC10377040/ /pubmed/37509687 http://dx.doi.org/10.3390/biomedicines11072048 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Zhaobin
Peng, Qingzhi
Liu, Weidong
Demongeot, Jacques
Wei, Dongqing
Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation
title Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation
title_full Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation
title_fullStr Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation
title_full_unstemmed Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation
title_short Antibody Dynamics Simulation—A Mathematical Exploration of Clonal Deletion and Somatic Hypermutation
title_sort antibody dynamics simulation—a mathematical exploration of clonal deletion and somatic hypermutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377040/
https://www.ncbi.nlm.nih.gov/pubmed/37509687
http://dx.doi.org/10.3390/biomedicines11072048
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