We demonstrate ex vivo in humans and in vivo in two different SLE-like mouse models that PD-L1 expression and IL-4 production by basophils are required to promote their cross-talk with TFH cells to sustain TFH cell pathogenic accumulation, TFH2 cell differentiation, and thereby mediate SLE disease onset and progression. Here, CD274 is linked to systemic lupus erythematosus.