TIGIT+ B cells: emerging immunoregulatory players in autoimmunity and transplantation tolerance with therapeutic potential.

T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor classically studied in T cells and natural killer (NK) cells. Recent evidence demonstrates that TIGIT is also expressed on distinct B cell subsets exhibiting potent immunoregulatory properties. TIGIT+ B cells are proposed to contribute to immune homeostasis through anti-inflammatory cytokine secretion, modulation of antigen-presenting cell function, regulation of T cell differentiation, and bidirectional crosstalk with regulatory T cells and myeloid populations. The strongest direct evidence for a role of TIGIT+ B cells in autoimmune pathogenesis exists in multiple sclerosis and type 1 diabetes, where these cells display regulatory activity and may help limit disease progression. In contrast, evidence in systemic lupus erythematosus, rheumatoid arthritis, and transplantation tolerance remains more limited and largely indirect, often inferred from broader regulatory B cell (Breg) biology, TIGIT studies in other immune cell types, or systemic pharmacologic interventions. This review summarizes the biology, phenotype, and proposed functions of TIGIT+ B cells. It also discusses emerging insights into their roles in autoimmunity and transplantation tolerance by explicitly distinguishing direct experimental findings from broader TIGIT-related data, and finally explores therapeutic strategies targeting TIGIT signaling, highlighting key challenges and opportunities for future research and clinical applications.