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 as a low-affinity receptor for IgE and as a ligand for the CD21 and CD11b/CD11c differentiation antigens. CD23 is released from the surface of cells as soluble fragments, and a 25-kD species of soluble CD23 (sCD23) appears to act as a multifunctional cytokine. In this report, sCD23 is shown to sustain the growth of low cell density cultures of a human pre-B-acute lymphocytic leukemia cell line, SMS-SB: no other cytokine tested was able to induce this effect. Flow cytometric analysis indicates that sCD23 acts to prevent apoptosis of SMS-SB cells. SMS-SB cells cultured at low cell density possess low levels of bcl-2 protein. Addition of sCD23 to cells at low cell density maintained bcl-2 expression at levels equivalent to those observed in SMS-SB cells cultured at higher cell densities. No CD23 mRNA was found in SMS-SB cells, ruling 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-containing liposomes, but not glycophorin-containing liposomes. Binding of CD23-containing liposomes is inhibited by anti-CD23 but not by anti-CD21 or anti-CD11b/c monoclonal antibodies. The data show that sCD23 prevents apoptosis of the SMS-SB cell line by acting through a novel receptor.
White
L J
LJ
Institute of Biomedical & Life Sciences, University of Glasgow, Scotland, UK.
Ozanne
B W
BW
Graber
P
P
Aubry
J P
JP
Bonnefoy
J Y
JY
Cushley
W
W
D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000473:pathology*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
D016207:Cytokines; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; D011971:Receptors, Immunologic