Germinal centers (GCs) provide a microenvironment that promotes and regulates the interactions of B cells with follicular Th (T FH) cells. In this study, we show that there are significantly higher frequencies of CXCR5+ ICOS+ T FH cells in autoimmune BXD2 mice, and these cells express both IL-21R and IL-17RA. Although IL-17 and IL-21 are both important for the formation of spontaneous GCs and development of pathogenic autoantibodies, IL-21, but not IL-17, is required for the proper development of T FH cells in BXD2 mice. The total numbers of T FH cells and their ability to induce B cell responses in vitro were not affected by a deficiency of IL-17RA in BXD2-Il17ra−/− mice, the majority of CXCR5+ T FH cells from BXD2-Il17ra−/− mice were, however, not localized in the GC light zone (LZ). Interruption of IL-17 signaling, either acutely by AdIL-17R: Fc or chronically by Il17ra−/−, disrupted T FH–B interactions and abrogated the generation of autoantibody-forming B cells in BXD2 mice. IL-17 upregulated the expression of regulator of G-protein signaling 16 (RGS16) to promote the ability of T FH to form conjugates with B cells, which was abolished in T FH cells from BXD2-Rgs16−/− mice. The results suggests that IL-17 is an extrinsic stop signal that it acts on postdifferentiated IL-17RA+ T FH to enable its interaction with responder B cells in the LZ niche. These data suggest a novel concept that T FH differentiation and its stabilization in the LZ are two separate checkpoints and that IL-21 and IL-17 act at each checkpoint to enable pathogenic GC development.