Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire
The adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B lymphocytes expressing high-affinity antigen receptors. However, this...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
American Physical Society
2023-05-01
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| Series: | Physical Review X |
| Online Access: | http://doi.org/10.1103/PhysRevX.13.021022 |
| _version_ | 1797829717339930624 |
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| author | Hongda Jiang Shenshen Wang |
| author_facet | Hongda Jiang Shenshen Wang |
| author_sort | Hongda Jiang |
| collection | DOAJ |
| description | The adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B lymphocytes expressing high-affinity antigen receptors. However, this rapid evolution inside an individual appears ineffective, hitting a modest ceiling of antigen-binding affinity. Only recently, experiments began to reveal that evolving B cells physically extract antigens from presenting cells using active forces, and that the extraction level dictates clonal fitness. These observations challenge the prevailing view that the equilibrium constant of receptor-antigen binding determines selective advantage of a B cell clone. Here, we present a theoretical framework to explore ways in which tug-of-war antigen extraction impacts the quality and diversity of an evolved B cell repertoire. We propose that the apparent “ineffectiveness” of in vivo selection can be a direct consequence of nonequilibrium antigen recognition. Our theory predicts, on the one hand, that the physical limits of antigen tether strength, under tugging forces, set the affinity ceiling. On the other hand, intriguingly, cells can use force heterogeneity to diversify binding phenotype without compromising fitness, thus remaining plastic under resource constraint. These results suggest that active probing of receptor quality—via a molecular tug of war during antigen recognition—limits the potency of response to current antigens, but confer adaptive benefit against future variants. By bridging physical mechanisms and evolved functions, this work reveals a multifaceted role of active forces in immune adaptation, which rationalizes key observations on repertoire dynamics. |
| first_indexed | 2024-04-09T13:25:46Z |
| format | Article |
| id | doaj.art-d1f92ca787754af59734eeebbe85da16 |
| institution | Directory Open Access Journal |
| issn | 2160-3308 |
| language | English |
| last_indexed | 2024-04-09T13:25:46Z |
| publishDate | 2023-05-01 |
| publisher | American Physical Society |
| record_format | Article |
| series | Physical Review X |
| spelling | doaj.art-d1f92ca787754af59734eeebbe85da162023-05-10T14:05:14ZengAmerican Physical SocietyPhysical Review X2160-33082023-05-0113202102210.1103/PhysRevX.13.021022Molecular Tug of War Reveals Adaptive Potential of an Immune Cell RepertoireHongda JiangShenshen WangThe adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B lymphocytes expressing high-affinity antigen receptors. However, this rapid evolution inside an individual appears ineffective, hitting a modest ceiling of antigen-binding affinity. Only recently, experiments began to reveal that evolving B cells physically extract antigens from presenting cells using active forces, and that the extraction level dictates clonal fitness. These observations challenge the prevailing view that the equilibrium constant of receptor-antigen binding determines selective advantage of a B cell clone. Here, we present a theoretical framework to explore ways in which tug-of-war antigen extraction impacts the quality and diversity of an evolved B cell repertoire. We propose that the apparent “ineffectiveness” of in vivo selection can be a direct consequence of nonequilibrium antigen recognition. Our theory predicts, on the one hand, that the physical limits of antigen tether strength, under tugging forces, set the affinity ceiling. On the other hand, intriguingly, cells can use force heterogeneity to diversify binding phenotype without compromising fitness, thus remaining plastic under resource constraint. These results suggest that active probing of receptor quality—via a molecular tug of war during antigen recognition—limits the potency of response to current antigens, but confer adaptive benefit against future variants. By bridging physical mechanisms and evolved functions, this work reveals a multifaceted role of active forces in immune adaptation, which rationalizes key observations on repertoire dynamics.http://doi.org/10.1103/PhysRevX.13.021022 |
| spellingShingle | Hongda Jiang Shenshen Wang Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire Physical Review X |
| title | Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire |
| title_full | Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire |
| title_fullStr | Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire |
| title_full_unstemmed | Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire |
| title_short | Molecular Tug of War Reveals Adaptive Potential of an Immune Cell Repertoire |
| title_sort | molecular tug of war reveals adaptive potential of an immune cell repertoire |
| url | http://doi.org/10.1103/PhysRevX.13.021022 |
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