Human marginal zone B cell development from early T2 progenitors.

Human marginal zone B cell development from early T2 progenitors.
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DOI:
10.1084/jem.20202001
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发表时间:
2021-04-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Spencer J
Spencer J
中科院分区:
其他
文献类型:
--
作者:
Tull TJ;Pitcher MJ;Guesdon W;Siu JHY;Lebrero-Fernández C;Zhao Y;Petrov N;Heck S;Ellis R;Dhami P;Kadolsky UD;Kleeman M;Kamra Y;Fear DJ;John S;Jassem W;Groves RW;Sanderson JD;Robson MG;D'Cruz DP;Bemark M;Spencer J

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本研究确定了从人类IgMhi肠道归巢过渡2细胞到边缘带B细胞的发育轨迹,严重系统性红斑狼疮患者的所有阶段都受到影响。B细胞从骨髓中作为过渡性(TS) B细胞出现,经过T1、T2和T3阶段分化为初始B细胞。我们已经确定了从T1阶段形成IgMhi和IgMlo发育轨迹的人B细胞成熟的分支。与IgMlo分支相比,IgMhi T2细胞α4β7整合素的表达较高,IL-4受体(IL4R)的表达较低,并被选择性募集到肠道相关淋巴组织。IgMhi T2细胞也与边缘带B细胞(MZBs)具有相同的转录组特征。通过对scrna测序数据的伪时间分析,确定了通过IgMhi轨迹从T1细胞到mzb的谱系进展。在严重SLE中观察到IgMhi归巢T2细胞频率降低,并与mzb及其推定的IgMhi前体减少有关。严重SLE患者肠道相关MZB成熟轴的崩溃证实了其在健康中的存在。
This study identifies a developmental trajectory from human IgMhi gut homing transitional 2 cells to marginal zone B cells, all stages of which are affected in patients with severe systemic lupus erythematosus. 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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