Anti-IL-21 treatment also led to a reduction in GC B cells, CD138<sup>hi</sup> plasmablasts, IFN-γ-dependent IgG2c production, and autoantibodies, indicating that Tfh cell-derived IL-21 is critical for pathological B cell cues in lupus.
T cells contribute to lupus pathogenesis by secreting pro-inflammatory cytokines such as IL-17, and by interacting with B cells and secreting helper factors such as IL-21 that promote production of IgG autoantibodies.
Addition of IL-21 to lupus autologous mixed lymphocyte cultures induced significant IgG production, and treatment with IL-21R.Fc to block IL-21/IL-21R interaction reduced the proportion of plasma cells.
Our data show for the first time that IL-21 has a pathogenic role in the MRL-Fas(lpr) lupus model by impacting B cell function and regulating the production of pathogenic autoantibodies.