In the study published in the journal Arthritis & Rheumatology on November 10 2023, entitled Single-cell profiling of bone marrow B cells uncovers early B cell developmental disorders associated with systemic lupus erythematosus, Prof. ZHANG Xiaoming’s group at the Shanghai Institute Immunity and Infection of the Chinese Academy of Sciences, Prof. GU Zhifeng at Affiliated Hospital of Nantong University, and Prof. SHENG Zizhang at Columbia University reported their new findings. The researchers revealed the immunological characteristics of bone marrow (BM) B cells in patients with systemic lupus erythematosus (SLE) and the potential mechanisms involved in their developmental disorders.

SLE is the prototypical autoimmune disease that affects millions of people worldwide, preferentially in young women, and can involve multiple organs and systems, leading to high morbidity and mortality. A hallmark of SLE is the breach of B cell self-tolerance, which leads to aberrant activation and the production of large amounts of autoantibodies. Current knowledge of SLE B cells is mainly derived from the peripheral blood, however, whether B cells develop aberrantly in the bone marrow is currently unclear in SLE patients. 

By applying single-cell sequencing (scRNA-seq, scBCR-seq) and high-dimensional immune profiling of BM and peripheral blood B cells from SLE patients and healthy donors, this study reported that BM early B cells were severely decreased in a subset of SLE patients (SLE EB^lo group). Further analysis indicated that the SLE EB^lo group had increased clinical disease activities, exacerbated symptoms, and elevated BM local and systemic inflammation compared to the BM early B cell normal SLE group (SLE EB^nor group).  

At molecular level, the SLE EB^lo group showed abnormal activation of type I interferon and metabolic signaling pathways, as well as dysregulated BCR repertoires in BM and peripheral blood B cells, compared with the SLE EB^nor group. Finally, the abnormalities of BM B cells from one patient of the SLE EB^lo group were essentially reversed after achieving clinical remission.