| Literature DB >> 33538776 |
Mats Bemark1,2, Jo Spencer3, Thomas J Tull3, Michael J Pitcher3, William Guesdon3, Jacqueline H Y Siu4, Cristina Lebrero-Fernández1, Yuan Zhao3, Nedyalko Petrov5, Susanne Heck5, Richard Ellis5, Pawan Dhami5, Ulrich D Kadolsky5, Michelle Kleeman5, Yogesh Kamra5, David J Fear3, Susan John3, Wayel Jassem6, Richard W Groves7, Jeremy D Sanderson8, Michael G Robson3, David P D'Cruz3.
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.Entities:
Mesh：
Substances：
Year: 2021 PMID： 33538776 PMCID： PMC7868795 DOI： 10.1084/jem.20202001
Source DB: PubMed Journal: J Exp Med ISSN： 0022-1007 Impact factor: 14.307