Abnormalities in the function of T and B lymphocytes and the signaling pathways induced through their receptors play a crucial role in the pathogenesis of SLE.114–117 Mice with B cell-specific RNF55 (c-Cbl) and RNF56 (Cbl-b) deficiency manifest spontaneously SLE-like disease.115 Cbl-dko B cells are not hyperactive in terms of proliferation and antibody production upon BCR stimulation both in vivo and in vitro. This evidence concerns the gene BCR and systemic lupus erythematosus.