Although deletion of IL-21R signaling had little impact on the elevated IL-17/IL-21-producing CD4+ T cells (hyper Th17 response) in Act1−/− mice, blockade of IL-21 diminished the B cell compartment and ameliorated the SLE- and Sjögren’s-like diseases in Act1-deficient mice. This evidence concerns the gene CD4 and systemic lupus erythematosus.