The following is a summary of “Interleukin 4-driven reversal of self-reactive B cell anergy contributes to the pathogenesis of systemic lupus erythematosus,” published in the October 2023 issue of Rheumatology by Liu et al. 

Systemic lupus erythematosus (SLE) is an autoimmune disease caused by the activation of anergic autoreactive B cells (B_ND cells). The exact mechanism by which these cells are reactivated has yet to be fully understood.

Researchers performed a retrospective study to elucidate the role of B_ND cells in SLE pathogenesis and their underlying mechanism.

The study conducted a comprehensive analysis, including phenotypic assessment, large-scale transcriptome analysis, and profiling of B cell receptor (BCR) repertoires at both the molecular and single-cell levels. They used samples from healthy individuals and SLE patients. In vitro, they treated isolated naïve B cells from peripheral blood with anti-CD79b monoclonal antibodies to induce anergy. They monitored IgM internalization using confocal microscopy and quantified it through flow cytometry.

The study demonstrated a reduction and disturbance in B_ND  cells among SLE patients. It showed that IL-4, an important cytokine, drove these pathological changes. The result also revealed that IL-4 reversed B cell anergy by promoting BCR recycling to the cell surface via STAT6 signaling.

The study found IL-4 reverses B cell anergy in SLE, suggesting that blocking IL-4 signaling could be a new treatment for SLE, with diagnostic and prognostic biomarkers to identify patients most likely to benefit.

Source: ard.bmj.com/content/82/11/1444