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 IL4 shows a poor capacity for CD23 expression on B-CLLs, we first examined the possible mechanisms underlying CD23 overexpression on BCLLs and found that mitogen-activated CLL T cells release soluble factors that are capable, in synergy with IL4, 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'y (potent inhibitor of CD23 on normal B cells), TNFa (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'y as well as IFNa, TNFa, 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 ofIL4. Inasmuch as optimal CD23 expression absolutely requires the combination of IFN'y, IL-2, TNFa (the production of which is increased in CLL disease), and IL4, it was relevant to show that IL4 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. (J.

The Utility of Flow Cytometric Immunophenotypic Analysis in the Distinction of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia From Mantle Cell Lymphoma

“…Several biologic activities are ascribed to CD23 and its soluble fragments, including regulation of normal B-and T-cell proliferation and control of IgE synthesis. 20 Increased levels of serum soluble fragments above that found in normal sera are also found in patients with CLL and have been shown to correlate with increasing Rai stage. 21 The precise function of CD23 or its soluble fragments in CLL is uncertain; however, data indicate that signaling through the surface CD23 molecule in B-cell CLL has a negative effect on the growth of the leukemic B cells, thus potentially explaining the more indolent nature of this disease.…”

“…20 It is mainly expressed on the surface of IgM and IgD positive resting B cells, but is also found on monocytes, T cells, follicular dendritic cells, Langerhans cells, platelets and eosinophils. Membrane bound CD23 is cleaved into soluble fragments (known as IgE binding factors).…”

Expression of a functional inducible nitric oxide synthase in hairy cell leukaemia and ESKOL cell line

“…Our group showed previously that the remission achieved by IFN-␣ treatment was correlated with a marked reduction in the serum level of soluble CD23 or sCD23 11 in agreement with the proposed role of CD23 and its soluble cleavage fragment in the proliferation and anti-apoptotic effect in chronic B cell malignancies. 12 The interleukin-1 (IL-1) family of agonists and antagonists is also involved in the regulation of HCL, as evidenced by the modulation of IL-1␤, IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptors type I and type II in HCL patients treated with 2-chloro-2Ј-deoxyadenosine (2-CdA). 13 However, there is evidence that tumoral cells accumulation in HCL may result from an imbalance between proliferation and deficient apoptosis.…”

Emerging Therapies in Chronic Lymphocytic Leukemia

“…The CD23 antigen is a low-affinity IgE receptor that is found in high levels in CLL patients (Fournier et al 1992). Lumiliximab inhibits the IgE secretion in vitro, binds complement and mediates ADCC by binding FcγRI and RII receptors.…”