T peripheral helper 1 cells effectively drive atypical double-negative CD11chi B cells to antibody-secreting cells and play a pathogenic role in systemic lupus erythematosus.

We investigated cytokine expression patterns and B cell-helper functions of T peripheral helper (Tph) cell subsets. CXCR3+CCR6- Tph1 cells have ability to co-produce interleukin (IL)-21 and interferon-γ while CXCR3-CCR6+ Tph17 can co-produce IL-21 and IL-17A. These Tph subsets show almost comparable activity to induce plasma cell differentiation from CD19+ B cells. Noticeably, Tph1 cells can drive plasma cell differentiation from CD11chi double negative (DN) B cells more effectively than classical memory B cells via IL-21. On the other hand, Tph17 cells appear to have low activity to induce plasma cell differentiation from CD11chi DN B cells. Furthermore, in new-onset patients with systemic lupus erythematosus (SLE), Tph1 cells are expanded in the blood and positively correlated with disease activity, autoantibody levels, and CD11chi B cells. These results suggest that extrafollicular interaction between Tph1 cells and atypical CD11chi DN B cells plays a pathogenic role in new-onset SLE.