There was a general consensus that pathologically increased BCR signaling contributed to B cell overactivity and autoimmunity, but recent studies showed that B cells in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS) displayed diminished phosphorylation of Syk and Btk upon BCR activation and share a phenotype of hyporesponsiveness toward BCR and TLR9 stimulation [1208-1210]. This evidence concerns the gene BTK and systemic lupus erythematosus.