CD4+ T cell activation of the non-canonical NF-κB pathway in CLL is also through CD40L activation of CD40 (58, 59) and, as a result, CD40L and IL4 are important components of laboratory-based co-culture systems which aim to mimic the tumor microenvironment (40, 60, 61). Here, CD40 is linked to B-cell chronic lymphocytic leukemia.