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Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints

In order to target threatening pathogens, the adaptive immune system performs a continuous reorganization of its lymphocyte repertoire. Following an immune challenge, the B cell repertoire can evolve cells of increased specificity for the encountered strain. This process of affinity maturation gener...

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Autores principales: Chardès, Victor, Vergassola, Massimo, Walczak, Aleksandra M., Mora, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872716/
https://www.ncbi.nlm.nih.gov/pubmed/35177475
http://dx.doi.org/10.1073/pnas.2113512119
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author Chardès, Victor
Vergassola, Massimo
Walczak, Aleksandra M.
Mora, Thierry
author_facet Chardès, Victor
Vergassola, Massimo
Walczak, Aleksandra M.
Mora, Thierry
author_sort Chardès, Victor
collection PubMed
description In order to target threatening pathogens, the adaptive immune system performs a continuous reorganization of its lymphocyte repertoire. Following an immune challenge, the B cell repertoire can evolve cells of increased specificity for the encountered strain. This process of affinity maturation generates a memory pool whose diversity and size remain difficult to predict. We assume that the immune system follows a strategy that maximizes the long-term immune coverage and minimizes the short-term metabolic costs associated with affinity maturation. This strategy is defined as an optimal decision process on a finite dimensional phenotypic space, where a preexisting population of cells is sequentially challenged with a neutrally evolving strain. We show that the low specificity and high diversity of memory B cells—a key experimental result—can be explained as a strategy to protect against pathogens that evolve fast enough to escape highly potent but narrow memory. This plasticity of the repertoire drives the emergence of distinct regimes for the size and diversity of the memory pool, depending on the density of de novo responding cells and on the mutation rate of the strain. The model predicts power-law distributions of clonotype sizes observed in data and rationalizes antigenic imprinting as a strategy to minimize metabolic costs while keeping good immune protection against future strains.
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spelling pubmed-88727162022-08-17 Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints Chardès, Victor Vergassola, Massimo Walczak, Aleksandra M. Mora, Thierry Proc Natl Acad Sci U S A Physical Sciences In order to target threatening pathogens, the adaptive immune system performs a continuous reorganization of its lymphocyte repertoire. Following an immune challenge, the B cell repertoire can evolve cells of increased specificity for the encountered strain. This process of affinity maturation generates a memory pool whose diversity and size remain difficult to predict. We assume that the immune system follows a strategy that maximizes the long-term immune coverage and minimizes the short-term metabolic costs associated with affinity maturation. This strategy is defined as an optimal decision process on a finite dimensional phenotypic space, where a preexisting population of cells is sequentially challenged with a neutrally evolving strain. We show that the low specificity and high diversity of memory B cells—a key experimental result—can be explained as a strategy to protect against pathogens that evolve fast enough to escape highly potent but narrow memory. This plasticity of the repertoire drives the emergence of distinct regimes for the size and diversity of the memory pool, depending on the density of de novo responding cells and on the mutation rate of the strain. The model predicts power-law distributions of clonotype sizes observed in data and rationalizes antigenic imprinting as a strategy to minimize metabolic costs while keeping good immune protection against future strains. National Academy of Sciences 2022-02-17 2022-02-22 /pmc/articles/PMC8872716/ /pubmed/35177475 http://dx.doi.org/10.1073/pnas.2113512119 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Physical Sciences
Chardès, Victor
Vergassola, Massimo
Walczak, Aleksandra M.
Mora, Thierry
Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
title Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
title_full Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
title_fullStr Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
title_full_unstemmed Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
title_short Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
title_sort affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872716/
https://www.ncbi.nlm.nih.gov/pubmed/35177475
http://dx.doi.org/10.1073/pnas.2113512119
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