T-bet expression in B cell subsets: Association with T peripheral helper cells and clinical activity in systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) features aberrant T-B cooperation and expansion of atypical memory B cells (aMBCs) characterized by the expression of CD11c and T-bet. We investigated the relationship between IL-21/IL-21R and the activation state of cTfh and Tph, with CD11c+T-bet + B cell subsets and clinical activity. Methods A cross-sectional study was conducted involving 40 patients with systemic lupus erythematosus (SLE) and 15 healthy subjects (HS). A multiparameter flow cytometry was used to evaluate Tph (CD4 + CXCR5 - PD-1 + ), cTfh (CD4 + CXCR5 + PD-1 + ), and aMBCs (CD19 + CXCR5 - CD11c + ) subsets and intracellular expression of IL-17A (iIL-17A), IL-21 (iIL-21), and T-bet. The disease activity was assessed using the SLEDAI-2K. Results We found an increased frequency of cTfh PD-1 vh , HLA-DR + , IL-21R + , and Tph PD-1 vh , HLA-DR + , and iIL-21 + cells in SLE patients. The aNAV T-bet + cells were expanded in SLE patients. Activated T-cell states (iIL-21 + /IL-21R + /PD-1 vh /HLA-DR + ) correlated with T-bet + B cells subsets. Finally, activated cTfh/Tph and aMBCs correlated with SLEDAI-2K. Conclusions Our findings provide new insights into the cooperative expression of IL-21/IL-21R and T-bet and their potential relationships with extrafollicular B-cell responses in SLE. These results highlight the IL-21/T-bet axis, offering potential avenues for biomarker development and targeted therapeutic intervention in SLE.