C3b receptors mediate the growth factor-induced proliferation of malignant B-chronic lymphocytic leukemia lymphocytes.
We have investigated the function of C3b receptor (CR1) in the malignant lymphocytes of B-chronic lymphocytic leukemia (B-CLL) mimicking the physiological ligand C3b with the anti-CR1 monoclonal antibody CB04 covalently linked to Sepharose CL-4B (CB04-S). The binding of insolubilized CB04-S to CR1 gave a progression signal to B-CLL cells which became B cell growth factor (BCGF)-responsive. The cells of 13 of 14 cases treated with CB04-S showed an active time-dependent proliferation when BCGF was added to the culture. After 72 hr of exposure to BCGF, the growth fraction evaluated with the Ki67 monoclonal antibody was 23.4 +/- 8.9 and the proportion of cells in S phase assessed by the bromodeoxyuridine incorporation technique was 18.6 +/- 8.5%. The proper sequence of CB04-S followed by BCGF was also important since the proliferation was halved when the sequence was reversed or the two signals were delivered concomitantly. CB04-S and BCGF alone failed to induce any significant proliferation; the percentage of cycling cells was less than 1% overlapping that of control culture cells. On the contrary, the proliferation of normal tonsil B cells was triggered both by CB04-S and by BCGF used as single agents (bromodeoxyuridine+ cells 12.7 +/- 5.1% and 20.0 +/- 7.3, respectively). Together these data indicate that malignant B-CLL cells need a sequential two-step signal based upon CR1 binding in order to be activated in vitro. This is a major difference with normal tonsil B lymphocytes whose proliferation is triggered both by CB04-S and by BCGF used as single agents.
D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d
D007378:Interleukins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D015847:Interleukin-4