INHIBITION OF APOPTOSIS IN A HUMAN PRE-B-CELL LINE BY CD23 IS MEDIATED VIA A NOVEL RECEPTOR

Human CD23 is a 45-kD type II membrane glycoprotein, which functions a s a low-affinity receptor for IgE and as a ligand for the CD21 and CD1 1b/CD11c differentiation antigens. CD23 is released from the surface o f cells as soluble fragments, and a 25-kD species of soluble CD23 (sCD 23) appears to act as a multifunctional cytokine. In this report, sCD2 3 is shown to sustain the growth of low cell density cultures of a hum an pre-B-acute lymphocytic leukemia cell line, SMS-SB: no other cytoki ne tested was able to induce this effect. Flow cytometric analysis ind icates that sCD23 acts to prevent apoptosis of SMS-SB cells. SMS-SB ce lls cultured at low cell density possess low levels of bcl-2 protein. Addition of sCD23 to cells at low cell density maintained bcl-2 expres sion at levels equivalent to those observed in SMS-SB cells cultured a t higher cell densities. No CD23 mRNA was found in SMS-SB cells, rulin g out an autocrine function for CD23 in this cell line model. Although SMS-SB cells do not express the known receptors for CD23, namely CD21 , CD11b-CD18, or CD11c-CD18, the cells specifically bind CD23-containi ng liposomes, but not glycophorin-containing liposomes, Binding of CD2 3-containing liposomes is inhibited by anti-CD23 but not by anti-CD21 or anti-CD11b/c monoclonal antibodies, The data show that sCD23 preven ts apoptosis of the SMS-SB cell line by acting through a novel recepto r. (C) 1997 by The American Society of Hematology.