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Human marginal zone B cell development from early T2 progenitors

Tull, Thomas J. ; Pitcher, Michael J. ; Guesdon, William ; Siu, Jacqueline H.Y. ; Lebrero-Fernández, Cristina ; Zhao, Yuan ; Petrov, Nedyalko ; Heck, Susanne ; Ellis, Richard and Dhami, Pawan , et al. (2021) In Journal of Experimental Medicine 218(4).
Abstract

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data.... (More)

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health.

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publishing date
type
Contribution to journal
publication status
published
in
Journal of Experimental Medicine
volume
218
issue
4
article number
e20202001
publisher
Rockefeller University Press
external identifiers
  • pmid:33538776
  • scopus:85101252634
ISSN
0022-1007
DOI
10.1084/JEM.20202001
language
English
LU publication?
no
additional info
Publisher Copyright: © 2021 Tull et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
id
5183ac29-abb8-4504-a72e-c4cabe0f844e
date added to LUP
2023-11-28 10:17:36
date last changed
2024-04-25 13:02:18
@article{5183ac29-abb8-4504-a72e-c4cabe0f844e,
  abstract     = {{<p>B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgM<sup>hi</sup> and IgM<sup>lo</sup> developmental trajectories. IgM<sup>hi</sup> T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgM<sup>lo</sup> branch and are selectively recruited into gut-associated lymphoid tissue. IgM<sup>hi</sup> T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgM<sup>hi</sup> trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgM<sup>hi</sup> gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgM<sup>hi</sup> precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health.</p>}},
  author       = {{Tull, Thomas J. and Pitcher, Michael J. and Guesdon, William and Siu, Jacqueline H.Y. and Lebrero-Fernández, Cristina and Zhao, Yuan and Petrov, Nedyalko and Heck, Susanne and Ellis, Richard and Dhami, Pawan and Kadolsky, Ulrich D. and Kleeman, Michelle and Kamra, Yogesh and Fear, David J. and John, Susan and Jassem, Wayel and Groves, Richard W. and Sanderson, Jeremy D. and Robson, Michael D. and D’Cruz, David P. and Bemark, Mats and Spencer, Jo}},
  issn         = {{0022-1007}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Experimental Medicine}},
  title        = {{Human marginal zone B cell development from early T2 progenitors}},
  url          = {{http://dx.doi.org/10.1084/JEM.20202001}},
  doi          = {{10.1084/JEM.20202001}},
  volume       = {{218}},
  year         = {{2021}},
}