Memory persistence and differentiation into antibody-secreting cells accompanied by positive selection in longitudinal BCR repertoires
- Skolkovo Institute of Science and Technology, Russian Federation
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
Abstract
The stability and plasticity of B cell-mediated immune memory ensures the ability to respond to the repeated challenges. We have analyzed the longitudinal dynamics of immunoglobulin heavy chain repertoires from memory B cells, plasmablasts, and plasma cells from the peripheral blood of generally healthy volunteers. We reveal a high degree of clonal persistence in individual memory B cell subsets, with inter-individual convergence in memory and antibody-secreting cells (ASCs). ASC clonotypes demonstrate clonal relatedness to memory B cells, and are transient in peripheral blood. We identify two clusters of expanded clonal lineages with differing prevalence of memory B cells, isotypes, and persistence. Phylogenetic analysis revealed signs of reactivation of persisting memory B cell-enriched clonal lineages, accompanied by new rounds of affinity maturation during proliferation and differentiation into ASCs. Negative selection contributes to both persisting and reactivated lineages, preserving the functionality and specificity of BCRs to protect against current and future pathogens.
Data availability
Sequencing data have been deposited in the ArrayExpress database (www.ebi.ac.uk/arrayexpress, acc. num. E-MTAB-11193). The code for repertoire analysis is available at https://github.com/amikelov/igh_subsets; the code for clonal lineage analysis is available at https://github.com/EvgeniiaAlekseeva/Clonal_group_analysis
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Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controlsEuropean Nucleotide Archive, PRJEB26509.
Article and author information
Author details
Dmitriy M Chudakov
Funding
Ministry of Science and Higher Education of the Russian Federation (075-15-2020-807)
- Dmitriy M Chudakov
Russian Foundation for Basic Research (20-34-90153)
- Evgeniia I Alekseeva
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Informed consent was obtained from each donor. The study was approved by the Local Ethical Committee of Pirogov Russian National Research Medical University, Moscow, Russia (abstract #190 18 Nov 2019).
Reviewing Editor
- Tomohiro Kurosaki, Osaka University, Japan
Version history
- Preprint posted: January 1, 2022 (view preprint)
- Received: April 8, 2022
- Accepted: September 11, 2022
- Accepted Manuscript published: September 15, 2022 (version 1)
- Accepted Manuscript updated: September 22, 2022 (version 2)
- Version of Record published: September 30, 2022 (version 3)
Copyright
© 2022, Mikelov et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Memory persistence and differentiation into antibody-secreting cells accompanied by positive selection in longitudinal BCR repertoires
eLife 11:e79254.
https://doi.org/10.7554/eLife.79254
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