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

aging antibody mathematical modeling negative selection positive selection self-tolerance somatic hypermutation

Journal

Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304

Informations de publication

Date de publication:
20 Jul 2023
Historique:
received: 30 06 2023
revised: 14 07 2023
accepted: 19 07 2023
medline: 29 7 2023
pubmed: 29 7 2023
entrez: 29 7 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37509687
pii: biomedicines11072048
doi: 10.3390/biomedicines11072048
pmc: PMC10377040
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Dezhou University
ID : 30101418

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Auteurs

Zhaobin Xu (Z)

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

Qingzhi Peng (Q)

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

Weidong Liu (W)

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

Jacques Demongeot (J)

Laboratory AGEIS EA 7407, Team Tools for e-Gnosis Medical, Faculty of Medicine, University Grenoble Alpes (UGA), 38700 La Tronche, France.

Dongqing Wei (D)

School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China.

Classifications MeSH