Single-Cell Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus
Single-Cell Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus
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DOI：
10.1002/art.42750
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发表时间：
2024-01-30
影响因子：
13.3
通讯作者：
Gu，Zhifeng
中科院分区：
文献类型：
--
作者：
Dong，Chen;Guo，Yicheng;Gu，Zhifeng
外周B细胞室在系统性红斑狼疮（SLE）中受到严重干扰，但B细胞是否在骨髓（BM）中异常发育在很大程度上是未知的。方法我们进行了BM B细胞的单细胞RNA/B细胞受体（BCR）测序和免疫分析，并将SLE患者分为两组：早期B细胞（前B和前B）正常（EBnor）和EB缺陷/低（EBlo）组。结果SLE-EBlo组表现出更严重的疾病活动性和促炎状态，I型干扰素信号传导和B细胞室内代谢途径的过度作用，和异常的BCR库。此外，在一名SLE患者谁是最初分类的SLE-EBlo组，早期B细胞缺乏症和相关的异常在很大程度上纠正在第二个BM样品在remission phase.ConclusionIn总结，这项研究表明，早期B细胞损失在BM定义一个独特的病理状态在一个子集的SLE患者，可能发挥积极作用的失调的自身免疫反应。
ObjectiveThe peripheral B cell compartment is heavily disturbed in systemic lupus erythematosus (SLE), but whether B cells develop aberrantly in the bone marrow (BM) is largely unknown.MethodsWe performed single‐cell RNA/B cell receptor (BCR) sequencing and immune profiling of BM B cells and classified patients with SLE into two groups: early B cell (Pro‐B and Pre‐B) normal (EBnor) and EB defective/low (EBlo) groups.ResultsThe SLE‐EBlogroup exhibited more severe disease activity and proinflammatory status, overaction of type I interferon signaling and metabolic pathways within the B cell compartment, and aberrant BCR repertoires compared with the SLE‐EBnorgroup. Moreover, in one patient with SLE who was initially classified in the SLE‐EBlogroup, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase.ConclusionIn summary, this study suggests that early B cell loss in BM defines a unique pathological state in a subset of patients with SLE that may play an active role in the dysregulated autoimmune responses.