NIK knockout results in defective LT-βR signaling and conditional deletion of NIK in adult mice results in defects in B cell activation and survival as well as defective signaling upon BAFF, anti-CD40 or anti-IgM stimulation (53, 60), which may indicate great promise of NIK inhibition in B cell malignancies that are largely dependent on microenvironmental signals, such as chronic lymphocytic leukemia (CLL). Here, CD40LG is linked to B-cell chronic lymphocytic leukemia.