Human marginal zone B cell development from early T2 progenitors

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; David D’Cruz; Mats Bemark

doi:10.1084/jem.20202001

Human marginal zone B cell development from early T2 progenitors

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 RobsonDavid D’Cruz, Mats Bemark

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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.

Original language	English
Article number	e20202001
Journal	Journal of Experimental Medicine
Volume	218
Issue number	4
Early online date	4 Feb 2021
DOIs	https://doi.org/10.1084/jem.20202001
Publication status	Published - 5 Apr 2021

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Human marginal zone B_TULL_Accepted21December2020_GREEN VoR (CC BY)Final published version, 9 MBLicence: CC BY

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Spencer, J., Tull, T., Pitcher, M., Guesdon, W., Siu, J. HY., Lebraro-Fernandez, C., Zhao, Y., Petrov, N., Heck, S., Ellis, R., Dhami, P., kadolsky, U., Kleeman, M., Kamra, Y., Fear, D., John, S., Jassem, W., Groves, R., Sanderson, J. D., ... Bemark, M. (2021). Human marginal zone B cell development from early T2 progenitors. Journal of Experimental Medicine, 218(4), Article e20202001. https://doi.org/10.1084/jem.20202001

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title = "Human marginal zone B cell development from early T2 progenitors",

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.",

author = "Jo Spencer and Thomas Tull and Michael Pitcher and William Guesdon and Siu, {jacqueline HY} and Cristina Lebraro-Fernandez and Yuan Zhao and Nedyalko Petrov and Susanne Heck and Richard Ellis and Pawandeep Dhami and ulrich kadolsky and Michelle Kleeman and Yogesh Kamra and David Fear and Susan John and Wayel Jassem and Richard Groves and Sanderson, {Jeremy D.} and Michael Robson and David D{\textquoteright}Cruz and Mats Bemark",

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doi = "10.1084/jem.20202001",

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Spencer, J , Tull, T , Pitcher, M , Guesdon, W, Siu, JHY, Lebraro-Fernandez, C, Zhao, Y, Petrov, N, Heck, S, Ellis, R, Dhami, P, kadolsky, U, Kleeman, M, Kamra, Y, Fear, D , John, S, Jassem, W, Groves, R, Sanderson, JD, Robson, M , D’Cruz, D & Bemark, M 2021, 'Human marginal zone B cell development from early T2 progenitors', Journal of Experimental Medicine, vol. 218, no. 4, e20202001. https://doi.org/10.1084/jem.20202001

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AU - Spencer, Jo

AU - Tull, Thomas

AU - Pitcher, Michael

AU - Guesdon, William

AU - Siu, jacqueline HY

AU - Lebraro-Fernandez, Cristina

AU - Zhao, Yuan

AU - Petrov, Nedyalko

AU - Heck, Susanne

AU - Ellis, Richard

AU - Dhami, Pawandeep

AU - kadolsky, ulrich

AU - Kleeman, Michelle

AU - Kamra, Yogesh

AU - Fear, David

AU - John, Susan

AU - Jassem, Wayel

AU - Groves, Richard

AU - Sanderson, Jeremy D.

AU - Robson, Michael

AU - D’Cruz, David

AU - Bemark, Mats

PY - 2021/4/5

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AB - 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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JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 4

M1 - e20202001

ER -

Human marginal zone B cell development from early T2 progenitors

Abstract

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