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Human marginal zone B cell development from early T2 progenitors

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Jo Spencer, Thomas Tull, Michael Pitcher, William Guesdon, jacqueline HY Siu, Cristina Lebraro-Fernandez, Yuan Zhao, Nedyalko Petrov, Susanne Heck, Richard Ellis, Pawandeep Dhami, ulrich kadolsky, Michelle Kleeman, Yogesh Kamra, David Fear, Susan John, Wayel Jassem, Richard Groves, Jeremy D. Sanderson, Michael Robson & 2 more David D’Cruz, Mats Bemark

Original languageEnglish
Article numbere20202001
JournalJournal of Experimental Medicine
Volume218
Issue number4
Early online date4 Feb 2021
DOIs
Accepted/In press21 Dec 2020
E-pub ahead of print4 Feb 2021
Published5 Apr 2021

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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. 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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