CD40/CD40L interaction stimulates B cells to migrate to the germinal center where they undergo SHM and CSR.81,82 CLL cells have been shown to be generally responsive to CD40 ligation, whereas CD40L stimulation has been shown to up-regulate inhibitor of apoptosis proteins such as survinin.83 However, Scielzo et al recently showed that CLL cells exhibit differential patterns of responsiveness upon in vitro CD40L stimulation, linked to distinct activation of intracellular signaling pathways (i.e. phoshorylation of IKKα/β, upregulation of BCL2, MCL1) and, intriguingly, to clinical outcome. This evidence concerns the gene BCL2 and B-cell chronic lymphocytic leukemia.