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.
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
Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controlsEuropean Nucleotide Archive, PRJEB26509.
- Dmitriy M Chudakov
- Evgeniia I Alekseeva
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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).
- Tomohiro Kurosaki, Osaka University, Japan
© 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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