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

BackgroundSystemic 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.MethodsA 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.ResultsWe 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.ConclusionsOur 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.