title: CD23 antigen regulation and signaling in chronic lymphocytic leukemia.
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.
authors.affiliation: Notre-Dame Hospital, University of Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Fournier
authors.forename: G
authors.initials: G
authors.lastname: Delespesse
authors.forename: M
authors.initials: M
authors.lastname: Rubio
authors.forename: G
authors.initials: G
authors.lastname: Biron
authors.forename: M
authors.initials: M
authors.lastname: Sarfati
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis* / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis* / Q000235:genetics; D017455:Receptors, IgE; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D007376:Interleukin-2; D012333:RNA, Messenger; D011961:Receptors, Fc; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D004247:DNA