CBLB and neoplasm: Further studies using Cbl-b E3 ligase-defective (C373Aki/Ki) knock in mice (91) revealed that selective genetic inactivation of Cbl-b ligase activity phenocopies the total loss of Cbl-b, resulting in hyperactivation of T cells, impaired induction of T cell anergy, spontaneous autoimmunity, and tumor rejection demonstrating that the catalytic function of Cbl-b is essential for negative regulation of T cells in vivo (35).