Medicine and Health

Understanding repertoire sequencing data through a multiscale computational model of the germinal center

R. García-valiente, E. M. Tejero, et al.

This study delves into B-cell and T-cell immune receptor repertoires, revealing surprising insights about clonal abundance and affinity variability. Fascinating simulations guide experimental design, enriching our understanding of the adaptive immune response. The research was conducted by Rodrigo García-Valiente, Elena Merino Tejero, Maria Stratigopoulou, Daria Balashova, Aldo Jongejan, Danial Lashgari, Aurélien Pélissier, Tom G. Caniels, Mathieu A. F. Claireaux, Anne Musters, Marit J. van Gils, María Rodríguez Martínez, Niek de Vries, Michael Meyer-Hermann, Jeroen E. J. Guikema, Huub Hoefsloot, and Antoine H. C. van Kampen.

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Index

Abstract

Sequencing of B-cell and T-cell immune receptor repertoires helps understand the adaptive immune response, but only provides information about clonotypes, frequencies, not affinity or antigen specificity. This study extends a multiscale germinal center (GC) model to gain insights into B-cell repertoires, comparing simulated repertoires with experimental data from single GCs, blood, or tissue. Simulations reveal limited correlation between clonal abundance and affinity, and large affinity variability among subclones. Low-abundance clones/subclones may have high affinity. Plasma cell (PC) fraction with high BCR mRNA content doesn't significantly affect dominant clone numbers from single GCs. These simulations guide data interpretation and experimental design.

Publisher

npj Systems Biology and Applications

Published On

Mar 16, 2023

Authors

Rodrigo García-Valiente, Elena Merino Tejero, Maria Stratigopoulou, Daria Balashova, Aldo Jongejan, Danial Lashgari, Aurélien Pélissier, Tom G. Caniels, Mathieu A. F. Claireaux, Anne Musters, Marit J. van Gils, María Rodríguez Martínez, Niek de Vries, Michael Meyer-Hermann, Jeroen E. J. Guikema, Huub Hoefsloot, Antoine H. C. van Kampen

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