B-Cell Plasticity in Autoimmune Diseases: Pathogenic Mechanisms and Emerging Biological Therapies
Year: 2026
Type: article
Abstract: B lymphocytes were long viewed mainly as precursors of antibody-secreting cells, yet their contribution to autoimmunity extends well beyond autoantibody production. Over the past two decades it has become clear that B cells are highly plastic: they shift between functional states in response to antigen, co-stimulatory signals, cytokines, innate sensors and metabolic cues. In health, this flexibility supports rapid, high-affinity and durable humoral immunity. In autoimmune disease, the same flexibility can be subverted, allowing autoreactive clones to escape tolerance checkpoints, acquire inflammatory phenotypes, present antigen to pathogenic T cells, secrete cytokines and differentiate into long-lived plasma cells that resist conventional immunosuppression. This review summarizes current knowledge of B-cell development and differentiation, the transcriptional, signalling and receptor-level mechanisms that govern B-cell fate, and the atypical, regulatory and effector subsets that have been described in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and related conditions. We discuss how B-cell and T-cell interactions, epigenetic remodelling and metabolic reprogramming consolidate pathogenic states, and how these processes culminate in autoantibody-mediated and cytokine-mediated tissue inflammation. We then examine established and emerging biological therapies, including anti-CD20 antibodies, BAFF-axis inhibitors, Bruton's tyrosine kinase inhibitors, plasma-cell-directed agents, neonatal Fc receptor blockade and CD19-directed chimeric antigen receptor T cells. Finally, we consider the limitations of current approaches and outline research priorities aimed at moving from broad depletion towards precise, durable and safe reprogramming of the B-cell compartment.
Institution: Fergana Medical Institute of Public Health
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225138485