Preliminary Analysis of the Proportion and Characteristics of Dual BCR B Cells in SLE Model Mice and Patients via scRNA-Seq Combined with scBCR-Seq Technology.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune dysregulation and multi-organ damage. Abnormal B cell activation and autoantibody production constitute the core pathological mechanism of SLE. However, the proportion, BCR pairing types, clonal evolution patterns, and transcriptomic features of dual BCR B cells in SLE remain incompletely elucidated. In this study, we employed single-cell RNA sequencing (scRNA-seq) combined with single-cell B cell receptor repertoire sequencing (scBCR-seq) to preliminarily analyze the proportion and characteristics of dual BCR B cells in SLE model mice (MRL/Lpr and SLE.Yaa) as well as in peripheral blood from SLE patients. The results showed: (1) Compared with control groups, the proportion of dual BCR B cells in SLE model mice and patients exhibited a decreasing trend, whereas the diversity of the CDR3 repertoire decreased and clonality increased. Increased clonal sharing was observed between single BCR B cells and dual BCR B cells. The main pairing types of dual BCR B cells were H + κ1 + κ2, H1 + H2 + κ, and H1 + H2 + κ + λ, with preferential utilization of autoimmunity-associated V gene families such as IGHV4-34, and high expression of IGHG subtypes. (2) Tracking analysis of B cell receptor clonality and effector molecule expression revealed that in SLE, dual BCR B cells tend to enrich in IFN-α/γ responses, TNF-NFκB inflammation, and complement pathways, and highly express interferon-related genes such as Ly6a, Isg15, MX1, and IFI6. (3) In both single BCR B and dual BCR B cells from SLE patients, the proportion of the naïve B cell subset decreased, whereas the proportions of plasma and Breg subsets increased and exhibited clonal expansion. SLE dual BCR Breg cells highly expressed IL10, HSPA1A, and others. This study is the first to reveal, at the high-throughput single-B-cell level, that the proportion, subset origin distribution, CDR3 repertoire composition, and effector molecule expression of dual BCR B cells display unique characteristics in SLE model mice and patients, providing baseline comparative data and novel research perspectives for further investigation into B cell effector functions and mechanisms in SLE patients.