作者
Chen Dong,Yicheng Guo,Zechuan Chen,Teng Li,Juan Ji,Chi Sun,Jing Li,Cao H,Yunfei Xia,Zhonghui Xue,Xianfeng Gu,Qian Liang,Rui Zhao,Ting Fu,Jiaqiang Ma,Shan Jiang,Chujun Wu,Qiong Fu,Genkai Guo,Yu Bao,Hua Guo,Junling Yang,Min Xu,Xiaoming Zhang,Zizhang Sheng,Zhifeng Gu
摘要
The 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.We 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.The SLE-EBlo group 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-EBnor group. Moreover, in one patient with SLE who was initially classified in the SLE-EBlo group, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase.In 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.