<scp>Single‐Cell</scp> Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus
Chen Dong, Yicheng Guo, Zechuan Chen, Teng Li, Juan Ji, Chi Sun, Jing Li, Haixia Cao, Yunfei Xia, Zhonghui Xue, Xixi Gu, Qian Liang, Rui Zhao, Ting Fu, Jiaqiang Ma, Shan Jiang, Chunmei Wu, Qiong Fu, Genkai Guo, Yanfeng Bao, Hua Guo, Junling Yang, Min Xu, Xiaoming Zhang, Zizhang Sheng, Zhifeng Gu
Abstract
Objective 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. Methods 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 (EB nor ) and EB defective/low (EB lo ) groups. Results The SLE‐EB lo 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‐EB nor group. Moreover, in one patient with SLE who was initially classified in the SLE‐EB lo group, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase. Conclusion 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.