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. 1992 Apr;89(4):1312–1321. doi: 10.1172/JCI115717

CD23 antigen regulation and signaling in chronic lymphocytic leukemia.

S Fournier 1, G Delespesse 1, M Rubio 1, G Biron 1, M Sarfati 1
PMCID: PMC442993  PMID: 1532590

Abstract

B lymphocytes from patients with chronic lymphocytic leukemia (B-CLLs), strongly express the CD23 antigen, a surface marker with significant prognostic importance in this disease. Because we previously reported that IL-4 shows a poor capacity for CD23 expression on B-CLLs, we first examined the possible mechanisms underlying CD23 overexpression on B-CLLs and found that mitogen-activated CLL T cells release soluble factors that are capable, in synergy with IL-4, of strongly inducing CD23. Using neutralizing Abs, we noticed that the T-cell-derived enhancing activity is entirely ascribed to the combined effects of IFN gamma (potent inhibitor of CD23 on normal B cells), TNF alpha (which has no effect on normal B cells), and IL-2 (which has a slight enhancing effect on both CLL and normal B cells). Furthermore, recombinant IFN gamma as well as IFN alpha, TNF alpha, and IL-2 (but not IL-3, IL-5, IL-6, IL-7, and lymphotoxin) significantly enhance CD23 protein and mRNA expression on B-CLLs, in the presence or absence of IL-4. Inasmuch as optimal CD23 expression absolutely requires the combination of IFN gamma, IL-2, TNF alpha (the production of which is increased in CLL disease), and IL-4, it was relevant to show that IL-4 mRNA is indeed expressed in fresh T-CLL cells. We next examined the possible role of CD23 in the regulation of B-CLL proliferation. Signaling through CD23 via ligation of the antigen by F(ab')2 anti-CD23 MAb but not Fab fragments inhibits the cytokine-induced B-CLL DNA synthesis. It is concluded that the CD23 gene is abnormally regulated in B-CLL disease and that cross-linking of CD23 molecule delivers a negative growth signal to the leukemic B cells.

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