REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
B Cell Receptor Signaling in Autoimmune Rheumatic Diseases: Regulatory 1 Mechanisms and Therapeutic Targeting
Yin Zhu 1
Lu Gao 1
Yu Han 1
Fucai Liu 1
Xin Xie 1
Xin Dai 2
Yufen Wang 2
Yimin Guo 1
Yan Chen 1
Pei Huang 1
Zuochen Du 1
1. Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China
2. Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, China
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Abstract
Abstract 21 Autoimmune rheumatic diseases (ARDs) are a diverse group of chronic disorders 22 characterized by immune dysregulation and multi-organ inflammation. B cell receptor 23 (BCR) signaling emerges as a shared, yet heterogeneously regulated, pathogenic axis 24 across these diseases. This dysregulation drives B cell activation, autoantibody 25 production, and ultimately tissue damage. Recent research highlights its involvement 26 in both common and disease-specific mechanisms, which helps explain the wide 27 variation in clinical features and therapeutic responses across ARDs. This review 28 summarizes current evidence establishing BCR signaling as a central regulatory and 29 therapeutic target in rheumatoid arthritis, systemic lupus erythematosus, Sjögren's 30 syndrome, IgG4-related disease, and ANCA-associated vasculitis. It integrates 31 mechanistic insights with recent clinical trial data on BCR signaling-targeted 32 therapies, discussing factors that may contribute to variability in therapeutic responses 33 and treatment limitations. Finally, we outline current challenges and future directions 34 for precision medicine in ARDs, with a focus on biomarker-guided strategies and 35 innovative combination therapies to improve patient outcomes.
Summary
Keywords
Autoimmune rheumatic diseases, B cell dysregulation, B cell receptor signaling, Combination therapies, kinase inhibitors, Pathogenesis, precision medicine, Therapeutic targeting
Received
20 November 2025
Accepted
27 January 2026
Copyright
© 2026 Zhu, Gao, Han, Liu, Xie, Dai, Wang, Guo, Chen, Huang and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Pei Huang; Zuochen Du
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