The increased signaling can derive from increased activity of signaling molecules in the BCR pathway (many of which are genetic risk factors for SLE; discussed below) (189), or through a synergy between BCR triggering and other signaling pathways, such as TLR, BAFF, and type I IFN, which can each lower the threshold for B cell activation through the BCR and contribute to the activation of B cells (59, 190, 191). This evidence concerns the gene BCR and systemic lupus erythematosus.