B Cells or T Cells in the Development and Sustenance of Rheumatoid Arthritis: Who is the Potential Contributor?

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterised by chronic joint inflammation driven by both cellular and humoral immune mechanisms. Autoantibodies and autoreactive lymphocytes play central roles in disease onset and progression. Although therapeutic strategies targeting T lymphocytes (T cells) and B lymphocytes (B cells) have benefited many patients, the precise cell type driving RA pathogenesis remains debated. In genetically predisposed individuals, immune tolerance is disrupted by environmental triggers such as smoking, infections, and stress. Antigen-driven adaptive immune responses dominate RA, with B cells undergoing clonal expansion and somatic hypermutation to produce high-affinity autoantibodies, notably anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF). Synovial inflammation exhibits diverse lymphocyte infiltration patterns, including diffuse inflammation (~50%), T-B cell aggregates with germinal centres (GC)~24%, and aggregates without GC ~20%. T cells within synovial tissue often display clonal restriction, enriched in memory and effector subsets such as CD4⁺ Th17, CD8⁺ resident memory, and innate-like T cells (γδ, MAIT, and NK cells), all contributing to persistent synovitis. Dysregulated cytokine signalling, particularly through the JAK/STAT pathway, characterises active disease. In ACPA-positive RA, autoantibodies enhance inflammation via innate immune activation, while B cells also function as antigen-presenting cells (APCs) that sustain T cell activation. However, in some patients, synovial autoimmunity may occur independently of GC formation or prominent B cell involvement, underscoring the disease's heterogeneity. This review highlights the evolving interplay between T and B cells from disease initiation to chronicity, which may help refine personalised immunotherapeutic approaches in RA.