Single‐Cell Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus

Abstract

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‐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.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.