Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates
- Sanquin, Netherlands
- University of Bonn, Germany
Abstract
Differentiation of B cells into antibody-secreting cells (ASCs) is a key process to generate protective humoral immunity. A detailed understanding of the cues controlling ASC differentiation is important to devise strategies to modulate antibody formation. Here, we dissected differentiation trajectories of human naive B cells into ASCs using single-cell RNA sequencing. By comparing transcriptomes of B cells at different stages of differentiation from an in vitro model with ex vivo B cells and ASCs, we uncovered a novel pre-ASC population present ex vivo in lymphoid tissues. For the first time, a germinal-center-like population is identified in vitro from human naive B cells and possibly progresses into a memory B cell population through an alternative route of differentiation, thus recapitulating in vivo human GC reactions. Our work allows further detailed characterization of human B cell differentiation into ASCs or memory B cells in both healthy and diseased conditions.
Data availability
All raw fastq files and digital gene expression matrixes (DGE) are available at the Gene Expression Omnibus (GEO) repository under accession no. GSE214265.
Article and author information
Author details
Niels JM Verstegen
Marieke SM van Ham
Funding
LSBR (1609)
- Marieke SM van Ham
PPOC (17-34/ L2263)
- Marieke SM van Ham
German research foundation (272482170)
- Marc Beyer
German research foundation (SFB1454-432325352)
- Marc Beyer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Murim Choi, Seoul National University, Republic of Korea
Ethics
Human subjects: All the healthy donors provided written informed consent following the protocol of the local institutional review board, the Medical Ethics Committee of Sanquin Blood Supply, and conforms to the principles of the Declaration of Helsinki.
Version history
- Received: September 20, 2022
- Preprint posted: October 5, 2022 (view preprint)
- Accepted: February 24, 2023
- Accepted Manuscript published: March 2, 2023 (version 1)
- Version of Record published: March 10, 2023 (version 2)
Copyright
© 2023, Verstegen 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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Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates
eLife 12:e83578.
https://doi.org/10.7554/eLife.83578
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