Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults in the Western world, which is characterized by an expansion of mature-appearing CD5+CD20lo B-cells showing an antigen-experienced CD27+, IgM+, and/or IgD+ unswitched phenotype, in association with either an unmutated (U-CLL) or mutated (M-CLL) B-cell receptor (BCR) (1). Here, CD40LG is linked to B-cell chronic lymphocytic leukemia.