Yongqi Liang,1,* Menglei Zha,1,* Qifeng Liu,1 Zhifei Lai,1 Lei Li,1 Yiming Shao,2 Jianbo Sun1 

1Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China; 2Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yiming Shao, Email sym@gdmu.edu.cn Jianbo Sun, Email jianbo.sun@gdmu.edu.cn

Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, joint destruction, and progressive disability. While current therapeutic approaches—including corticosteroids, disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and biologic agents—provide symptomatic relief, their clinical utility remains constrained by substantial limitations such as systemic toxicity, drug resistance, and cumulative adverse effects. These challenges underscore the critical need for novel therapeutic strategies with improved safety and efficacy profiles. The pathogenesis of RA involves multifaceted immune dysregulation, with emerging evidence highlighting the central role of B lymphocytes in both disease initiation and progression. Although B cell-targeted therapies like rituximab demonstrate clinical efficacy, unanswered questions persist regarding the precise immune functions of B cell subpopulations in RA pathogenesis and their potential as translatable therapeutic targets. This comprehensive review examines the clinical burden of RA, limitations of conventional therapies, and the evolving understanding of B cell pathophysiology. We critically evaluate established B cell-directed interventions—including B cell depletion, B cell functional modulation, and regulatory B cell (Breg) promotion—while exploring innovative nanofabrication technologies that may overcome current therapeutic barriers. By synthesizing recent advances in immunomodulatory research, this analysis aims to inform future directions for targeted RA management.

Keywords: RA, B cells, targeted therapy, immune regulation, antigen presentation