A new apoptotic pathway for the complement factor B-derived fragment Bb

Apoptosis is involved in both the cellular and humoral immune system destro ying tumors. An apoptosis-inducing factor from HL-60 myeloid leukemia cells was obtained, purified, and sequenced. The protein found has been identifi ed as a human complement factor B-derived fragment Bb, although it is known that factor B is able to induce apoptosis in several leukemia cell lines. Monoclonal antibodies against fragment Ba and Bb inhibited the apoptotic ac tivity of factor B. When the purified fragment Bb was used for apoptosis in duction, only the anti-Bb antibody inhibited Bb-induced apoptosis, and not the anti-Ba antibody. The apoptosis-inducing activity was found to be enhan ced under conditions facilitating the formation of Bb. Blocking TNF/TNFR or FasL/Fas interactions did not interfere with the factor B-induced apoptosi s. CD11c (iC3bR) acts as the main subunit of a heterodimer binding to fragm ent Bb in the apoptosis pathway, and the factor B-derived fragment Bb was f ound to possess the previously unknown function of inducing apoptosis in le ukemic cells through a suicide mechanism of myeloid lineage cells during th e differentiation stage. (C) 2000 WileY-Liss, Inc.