Considering that in vivo there are 0.5 to 3% newly born CLL cells per day [2] and 2–7% Ki67+ CLL cells in lymph node biopsies [3], it is plausible that co-culture with HS5-CD40L-IL4 might more closely resemble the moderate in vivo CLL cell proliferation rate, while the triple combination (HS5-CD40L-IL4-IL21) could technically be a more robust model useful in identifying anti-proliferative drugs (see below). This evidence concerns the gene CD40LG and B-cell chronic lymphocytic leukemia.