Different B cell subpopulations show distinct patterns in their IgH repertoire metrics
- University Children's Hospital, University of Zurich (UZH), Switzerland
- University of Oxford, United Kingdom
- Alchemab Ltd, United Kingdom
Abstract
Several human B-cell subpopulations are recognized in the peripheral blood, which play distinct roles in the humoral immune response. These cells undergo developmental and maturational changes involving VDJ recombination, somatic hypermutation and class switch recombination, altogether shaping their immunoglobulin heavy chain (IgH) repertoire. Here, we sequenced the IgH repertoire of naïve, marginal zone, switched and plasma cells from 10 healthy adults along with matched unsorted and in silico separated CD19+ bulk B cells. Using advanced bioinformatic analysis and machine learning, we show that sorted B cell subpopulations are characterised by distinct repertoire characteristics on both the individual sequence and the repertoire level. Sorted subpopulations shared similar repertoire characteristics with their corresponding in silico separated subsets. Furthermore, certain IgH repertoire characteristics correlated with the position of the constant region on the IgH locus. Overall, this study provides unprecedented insight over mechanisms of B cell repertoire control in peripherally circulating B cell subpopulations.
Data availability
Raw data used in this study are available at the NCBI Sequencing Read Archive (www.ncbi.nlm.nih.gov/sra) under BioProject number PRJNA748239 including metadata meeting MiAIRR standards (32). The processed dataset is available in Zenodo (https://doi.org/10.5281/zenodo.3585046) along with the protocol describing the exact processing steps with the software tools and version numbers.
Article and author information
Author details
Funding
Swiss National Science Foundation (PZ00P3_161147)
- Johannes Trück
Swiss National Science Foundation (PZ00P3_183777)
- Johannes Trück
Gottfried und Julia Bangerter-Rhyner-Stiftung
- Johannes Trück
Olga Mayenfisch Stiftung
- Johannes Trück
Palatin-Stiftung
- Johannes Trück
Biotechnology and Biological Sciences Research Council (BB/M011224/1)
- Aleksandr Kovaltsuk
UCB Pharma Ltd
- Aleksandr Kovaltsuk
Royal Commission for the Exhibition of 1851 Industrial Fellowship
- Aleksandr Kovaltsuk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Buffy coat samples were obtained from 10 anonymous healthy adults, hence no approval from the local ethics committee was necessary.
Copyright
© 2021, Ghraichy 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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Different B cell subpopulations show distinct patterns in their IgH repertoire metrics
eLife 10:e73111.
https://doi.org/10.7554/eLife.73111
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