Role for low-affinity receptor for IgE (CD23) in normal and leukemic B-cell proliferation.
CD23 gene is overexpressed and abnormally regulated in the most frequent adult leukemic disorder, B chronic lymphocytic leukemia (B-CLL). Switch on and off in the upregulation of surface CD23 expression consistently occurs in the early stage of normal B-cell activation, suggesting a key role for CD23 in this process. We show here that, after ligation of mlg in the presence of interleukin-4, the increase of CD23 protein precedes B-cell DNA synthesis and mainly results from the strong induction of CD23 type-B isoform. Exposure of normal B cells to conventional or phosphorothioate-derivatized CD23 antisense oligonucleotides (predominantly type B) significantly augments B-cell proliferation induced by antigen receptor stimulation or direct contact with activated T cells. Unexpectedly, CD23 antisense, but not sense, oligonucleotides specifically enhance rather than suppress CD23 expression on B cells. Finally, a selective increase in CD23 type-B expression provokes the entry of resting (Go) CLL B cells into G1 and S phase of the cell cycle in the absence of any other stimulus, whereas it synergizes with tumor necrosis factor-alpha to increase the number of activated B cells. These results provide compelling evidence that CD23 represents an important molecule directly involved in the process of normal or leukemic B-cell activation and growth.
Fournier
S
S
Allergy Research Laboratory, Notre-Dame Hospital Research Center, University of Montreal, Canada.
Rubio
M
M
Delespesse
G
G
Sarfati
M
M
D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000502:physiology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000502:physiology*
D004273:DNA, Neoplasm; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017455:Receptors, IgE