Back to Search Start Over

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

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
Source :
npj Systems Biology and Applications, Vol 9, Iss 1, Pp 1-14 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

Abstract Sequencing of B-cell and T-cell immune receptor repertoires helps us to understand the adaptive immune response, although it only provides information about the clonotypes (lineages) and their frequencies and not about, for example, their affinity or antigen (Ag) specificity. To further characterize the identified clones, usually with special attention to the particularly abundant ones (dominant), additional time-consuming or expensive experiments are generally required. Here, we present an extension of a multiscale model of the germinal center (GC) that we previously developed to gain more insight in B-cell repertoires. We compare the extent that these simulated repertoires deviate from experimental repertoires established from single GCs, blood, or tissue. Our simulations show that there is a limited correlation between clonal abundance and affinity and that there is large affinity variability among same-ancestor (same-clone) subclones. Our simulations suggest that low-abundance clones and subclones, might also be of interest since they may have high affinity for the Ag. We show that the fraction of plasma cells (PCs) with high B-cell receptor (BcR) mRNA content in the GC does not significantly affect the number of dominant clones derived from single GCs by sequencing BcR mRNAs. Results from these simulations guide data interpretation and the design of follow-up experiments.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
20567189
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
npj Systems Biology and Applications
Publication Type :
Academic Journal
Accession number :
edsdoj.44b6c99bb69541cc9cb23059ccbecc30
Document Type :
article
Full Text :
https://doi.org/10.1038/s41540-023-00271-y