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Understanding repertoire sequencing data through a multiscale computational model of the germinal center
Rodrigo García-Valiente1,2,3, Elena Merino Tejero1,2,3, Maria Stratigopoulou4,5
1Amsterdam UMC location University of Amsterdam, Epidemiology and Data Science, Meibergdreef 9, Amsterdam, The Netherlands.
NPJ Systems Biology and Applications
|March 17, 2023
Summary
Sequencing immune receptors reveals B-cell and T-cell clones but not their affinity. Our model shows low-abundance clones may have high affinity, suggesting new experimental directions for adaptive immunity research.
Area of Science:
- Immunology
- Computational Biology
- Bioinformatics
Background:
- Immune receptor repertoire sequencing identifies B-cell and T-cell clonotypes and frequencies.
- Characterizing identified clones, especially dominant ones, often requires extensive experiments.
- Existing methods lack direct insights into B-cell clone affinity or antigen specificity.
Purpose of the Study:
- To extend a multiscale germinal center (GC) model for deeper B-cell repertoire analysis.
- To compare simulated repertoires with experimental data from GCs, blood, and tissues.
- To investigate the relationship between clonal abundance, affinity, and subclone variability.
Main Methods:
- Development and application of an extended multiscale computational model of the germinal center.
- Simulation of B-cell repertoires and comparison with experimental repertoire data.
- Analysis of clonal abundance, affinity, and subclone characteristics within simulated repertoires.
Main Results:
- Limited correlation observed between B-cell clone abundance and affinity.
- Significant affinity variability exists among subclones derived from the same ancestor clone.
- Low-abundance clones and subclones may possess high antigen affinity.
- The proportion of plasma cells with high B-cell receptor mRNA in the GC minimally impacts dominant clone numbers.
Conclusions:
- Clonal abundance alone is an insufficient predictor of B-cell clone affinity.
- Low-frequency B-cell clones warrant further investigation for potential high-affinity interactions.
- Simulation results provide valuable guidance for interpreting experimental repertoire data and designing future studies.
