B cells in systemic lupus erythematosus: from pathogenic mechanisms to targeted therapies

Systemic lupus erythematosus (SLE) is a multisystem autoimmune condition characterized by a pronounced female predilection, particularly during reproductive age, and poses a significant threat to health and survival. A defining pathological feature is the production of autoantibodies by B lymphocytes, leading to the formation of immune complexes that deposit in various tissues and drive inflammation, thereby establishing the pivotal role of B cells in disease pathogenesis. Consistent observational and mechanistic studies have documented significant alterations in peripheral B cell subsets in SLE patients. These cells exhibit a state of hyperactivity and undergo aberrant differentiation, processes modulated by a complex interplay of pro-inflammatory cytokines, dysregulated transcription factor activity, and intracellular signaling pathway dysfunction. Multiple B cell-directed biological agents have undergone rigorous evaluation in both preclinical models and clinical trials. While some of these treatments have demonstrated promising efficacy, many others have often shown suboptimal therapeutic outcomes, highlighting an unmet need for more effective B cell-targeted interventions. This review synthesizes contemporary insights into the fundamental biology of B cells in SLE, integrating recent advances to refine the mechanistic understanding of their contribution to the disease. Furthermore, it critically appraises current and emerging B cell-targeted therapeutic strategies, assessing their translational potential and future directions in the management of SLE.