Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia.

CD5-expressing B lymphocytes from patients with selected chronic lymphoproliferative disorders were used to determine whether monoclonal populations of CD5+ human B cells produce autoantibodies. CD5+ B cells from 19 patients with chronic lymphocytic leukemia (CLL) and one with diffuse well-differentiated lymphocytic lymphoma (DWDL) were cultured, with and without mitogenic stimulation, to obtain Ig from these cells. 17 of the 20 samples produced Ig in vitro. mAb from nine of the 17 patients were reactive with either IgG, ssDNA, or dsDNA. In every instance, the autoantibodies displayed monotypic L chain usage that correlated precisely with the L chain expressed on the CD5+ leukemic B cell surface. These monoclonal autoantibodies varied in their degree of antigenic specificity; some were quite specific, reacting with only one antigen, whereas others were polyspecific, reacting with two or all three autoantigens tested. Three features distinguish these autoantibodies from those observed in prior studies of CD5+ B cells. First, they are clearly the products of monoclonal populations of CD5+ cells; second, several react with dsDNA, a specificity not previously reported and often seen in association with significant autoimmune disorders; and third, two of the monoclonal autoantibodies secreted by the CD5+ clones were of the IgG class. Although not all of the Ig-producing, CD5-expressing clones elaborated mAbs reactive with the autoantigens tested, greater than 50% did. It is possible that with a broader autoantigenic panel or with larger quantities of CLL/DWDL-derived Ig, even more autoantibody-producing clones might be identified. These studies may have important implications for the antigenic specificity of subsets of human B lymphocytes as well as for lymphoproliferative and autoimmune disorders in general.

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Chronic Lymphocytic Leukemia Associated with Autoimmune Diseases Often Discloses Activated Phenotype Pattern.

Blood ◽

10.1182/blood.v104.11.4802.4802 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4802-4802

Author(s):

Adrian Duek ◽

Lev Shvidel ◽

Alain Berrebi ◽

Osnat Bairey ◽

Andre Braester ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

Autoimmune Diseases ◽

B Lymphocytes ◽

De Novo ◽

Autoimmune Disorders ◽

Lymphocytic Leukemia ◽

Activation Markers ◽

Activated Lymphocytes ◽

Positive Direct

Abstract In autoimmune diseases the production of auto reactive antibodies is related to activation of normal B-lymphocytes. The high incidence of autoimmune disorders (AID) in CLL is well known, but the origin of auto antibodies is controversial. In the present study we postulate that Chronic Lymphocytic Leukemia associated with autoimmune diseases discloses activated phenotype pattern. Out of the 891 CLL patients registered in the Israeli Study Group, we found 72 patients (8%) who presented at least one clinically expressed autoimmune disease at diagnosis. Median age was 67 years old (range 45–87). 44% were male, 45 patients were at Binet`s stage A, 17 patients at Stage B and 4 at Stage C, and six patients were diagnosed with de novo PLL. The autoimmune disorders were as follows: Hashimoto`s disease (25), AIHA (11), Sjogren`s syndrome (10), rheumatoid arthritis (9), vasculitis (8), Grave’s disease (5), Evan’s syndrome (4), ITP (4), multiple sclerosis (2) and pernicious anemia, pure red cells aplasia, Raynaud`s syndrome, systemic erythematous lupus, ulcerative colitis (each-one). We found also 19 cases of positive direct antiglobulin test, 7 cases of positive rheumatoid factor, 4 cases with positive antinuclear antibodies, and 7 cases of hypocomplementemia. In 16 patients (22%) the morphology cell was consistent with activated lymphocytes (more than 30% of prolymphocytes). Immunophenotype analysis revealed increased expression (>30%) of activation markers CD38 or FMC7 in 27%. IgG was higher than 1000 mg/dl in 57%, while 5 cases found with IgM paraproteinemia. Increased Beta2- microglobulin level, described by us correlating the activation of B-CLL cells, was increased in 78% of tested cases. The new marker ZAP 70 analyzed in seven patients and found positive in 5. Interestingly, Beta2m and CD38 wich usually define agressive disease were found predominatly in stage A patients with AID. Our results suggest that in B- CLL associated with autoimmune disorders, the B CLL cells present some degree of activation. It is well known that B-lymphocytes in CLL are in a preactivated state and can be induced to differentiate into plasma cells and to stimulate residual normal B cells to produce high-affinity polyclonal autoantibodies with restricted specificity and pathogenic properties. This possibility would be in keeping with our observation. Conclusion: our data showing activated lymphocytes morphology and /or increased expression CD38 or FMC7, high level of IgG and of Beta2-m in most of the cases, suggests that a state of activation of B-cells may correlate with the occurrence of autoimmune complication in B-CLL.

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Interleukin-15 promotes the growth of leukemic cells of patients with B- cell chronic lymphoproliferative disorders

Blood ◽

10.1182/blood.v87.8.3327.bloodjournal8783327 ◽

1996 ◽

Vol 87 (8) ◽

pp. 3327-3335 ◽

Cited By ~ 61

Author(s):

L Trentin ◽

A Cerutti ◽

R Zambello ◽

R Sancretta ◽

C Tassinari ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Nk Cell ◽

Lymphoproliferative Disorders ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Interleukin 15

The recently discovered cytokine, interleukin-15 (IL-15), has been demonstrated to share several biologic properties with IL-2 in different cell systems, including T-cell and natural killer (NK) cell compartments. As for B lymphocytes, IL-15 has been shown to provide stimulatory activities in normal preactivated B cells that are mainly transduced through IL- 2 receptor (IL-2R) complex components. Since leukemic B cells from patients with chronic lymphoproliferative disorders (CLD) bear IL-2R and grow in response to IL-2, we investigated whether IL-15 triggers the proliferation of malignant B cells obtained from 12 patients with B-cell chronic lymphocytic leukemia (B-CLL) and five patients with hairy cell leukemia (HCL). Enriched B cells recovered from five healthy subjects were also studied as controls. IL-15 stimulated the proliferation of freshly isolated leukemic B cells, but not resting normal B lymphocytes, the latter being able to grow in the presence of IL-15 only after in vitro preactivation with phorbol myristate acetate. The proliferation elicited by IL-2 on leukemic cells was comparable to that determined by IL-15. Following addition of graded concentrations of IL-15 to low/intermediate-dose IL-2, resting leukemic B cells showed a higher stimulatory rate than that observed using the two cytokines separately. In normal resting B lymphocytes, this cumulative effect was not observed. The role of different IL-2R subunits in IL-15-driven growth of malignant B cells was investigated both by their expression on leukemic cells and by the block of different IL-2R subunits (p55, p75, and p64) with specific monoclonal antibodies (MoAbs). Using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses we demonstrated that both B-CLL and HCL leukemic B cells express the beta and gamma chains of the IL-2R system. The stimulatory activity achieved by IL-15 decreased significantly, blocking the beta and gamma chains of the IL-2R. Taken together, these findings demonstrate that IL-15 triggers the growth of leukemic B cells through IL-2R system subunits, pointing to the role of this novel cytokine in regulating the neoplastic proliferation in CLD.

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AB0024 IN VITRO CHARACTERIZATION OF CENERIMOD, A POTENT AND SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR 1 (S1P1) MODULATOR IN PREVENTING MIGRATION OF NON-ACTIVATED AND ACTIVATED PRIMARY HUMAN B CELLS IN THE PRESENCE OR ABSENCE OF GLUCOCORTICOIDS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2482 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1046.1-1046

Author(s):

L. Schlicher ◽

P. Kulig ◽

M. Murphy ◽

M. Keller

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Cell Activation ◽

Surface Expression ◽

Cell Surface Expression ◽

B Cell Activation ◽

Human B Cells ◽

Circulating Lymphocytes

Background:Cenerimod is a potent, selective, and orally active sphingosine 1-phosphate receptor 1 (S1P1) modulator that is currently being evaluated in a Phase 2b study in patients with systemic lupus erythematosus (SLE) (NCT03742037). S1P1 receptor modulators sequester circulating lymphocytes within lymph nodes, thereby reducing pathogenic autoimmune cells (including B lymphocytes) in the blood stream and in inflamed tissues. Extensive clinical experience has become available for the nonselective S1P receptor modulator fingolimod in relapsing forms of multiple sclerosis, supporting this therapeutic concept for the treatment of autoimmune disorders.Objectives:Although the effect of S1P-receptor modulators in reducing peripheral B cells is well documented1,2, the role of the S1P1 receptor on this cell type is only incompletely understood. In this study, the mode of action of cenerimod on primary human B cells was investigated in a series of in vitro experiments, including S1P1 receptor cell surface expression and chemotaxis towards S1P. Moreover, S1P1 expression following B cell activation in vitro was studied. As glucocorticoids (GC) are frequently used in the treatment of patients with autoimmune disorders including SLE, the potential influence of GC on the mode of action of cenerimod was evaluated.Methods:Primary human B lymphocytes from healthy donors were isolated from whole blood. In one set of experiments, cells were treated with different concentrations of cenerimod to measure S1P1 receptor internalization by flow cytometry. In a second set of experiments, isolated B cells were activated using different stimuli or left untreated. Cells were then analysed for S1P1 and CD69 cell surface expression and tested in a novel real-time S1P-mediated migration assay. In addition, the effect of physiological concentrations of GCs (prednisolone and prednisone) on cenerimod activity in preventing S1P mediated migration was tested.Results:In vitro, cenerimod led to a dose-dependent internalization of the S1P1 receptor on primary human B lymphocytes. Cenerimod also blocked migration of nonactivated and activated B lymphocytes towards S1P in a concentration-dependent manner, which is in line with the retention of lymphocytes in the lymph node and the reduction of circulating lymphocytes observed in the clinical setting. Upon B cell activation, which was monitored by CD69 upregulation, a simultaneous downregulation of S1P1 expression was detected, leading to less efficient S1P-directed cell migration. Importantly, physiological concentrations of GC did not affect the inhibitory activity of cenerimod on B cell migration.Conclusion:These results show that cenerimod, by modulating S1P1, blocks B lymphocyte migration towards its natural chemoattractant S1P and demonstrate compatibility of cenerimod with GC. These results are consistent with results of comparable experiments done previously using primary human T lymphocytes.References:[1]Nakamura M et al., Mult Scler. 2014 Sep; 20(10):1371-80.[2]Strasser DS et al., RMD Open 2020;6:e001261.Disclosure of Interests:None declared

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Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

Scientific Reports ◽

10.1038/s41598-021-92412-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ana Colado ◽

Esteban Enrique Elías ◽

Valeria Judith Sarapura Martínez ◽

Gregorio Cordini ◽

Pablo Morande ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Chronic Lymphocytic Leukemia ◽

T Cell Activation ◽

Cell Activation ◽

Lymphocytic Leukemia ◽

Immunomodulatory Effects ◽

Immunoglobulin Preparations

AbstractHypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

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Defective T cell-mediated, isotype-specific immunoglobulin regulation in B cell chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v71.4.1012.bloodjournal7141012 ◽

1988 ◽

Vol 71 (4) ◽

pp. 1012-1020 ◽

Cited By ~ 1

Author(s):

JS Moore ◽

MB Prystowsky ◽

RG Hoover ◽

EC Besa ◽

PC Nowell

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Cell Activity ◽

Lymphocytic Leukemia ◽

Specific Immunoglobulin ◽

Cell Chronic Lymphocytic Leukemia

The consistent occurrence of T cell abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that the non- neoplastic host T cells may be involved in the pathogenesis of this B cell neoplasm. Because potential defects of immunoglobulin regulation are evident in B-CLL patients, we investigated one aspect of this by studying the T cell-mediated immunoglobulin isotype-specific immunoregulatory circuit in B-CLL. The existence of class-specific immunoglobulin regulatory mechanisms mediated by Fc receptor-bearing T cells (FcR + T) through soluble immunoglobulin binding factors (IgBFs) has been well established in many experimental systems. IgBFs can both suppress and enhance B cell activity in an isotype-specific manner. We investigated the apparently abnormal IgA regulation in a B-CLL patient (CLL249) whose B cells secrete primarily IgA in vitro. Enumeration of FcR + T cells showed a disproportionate increase in IgA FcR + T cells in the peripheral blood of this patient. Our studies showed that the neoplastic B cells were not intrinsically unresponsive to the suppressing component of IgABF produced from normal T cells, but rather the IgABF produced by the CLL249 host T cells was defective. CLL249 IgABF was unable to suppress IgA secretion by host or normal B cells and enhanced the in vitro proliferation of the host B cells. Size fractionation of both normal and CLL249 IgABF by gel-filtration high- performance liquid chromatography (HPLC) demonstrated differences in the ultraviolet-absorbing components of IgABF obtained from normal T cells v that from our patient with defective IgA regulation. Such T cell dysfunction may not be restricted to IgA regulation, since we have found similar expansion of isotype-specific FcR + T cells associated with expansion of the corresponding B cell clone in other patients with B-CLL. These data suggest that this T cell-mediated regulatory circuit could be significantly involved in the pathogenesis of B-CLL.

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Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival

Blood ◽

10.1182/blood-2002-02-0558 ◽

2002 ◽

Vol 100 (8) ◽

pp. 2973-2979 ◽

Cited By ~ 164

Author(s):

Anne J. Novak ◽

Richard J. Bram ◽

Neil E. Kay ◽

Diane F. Jelinek

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

B Lymphocyte ◽

Leukemic Cell ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Aberrant Expression ◽

B Lymphocyte Stimulator

B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.

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Chronic Lymphocytic Leukemia B Cells Are Resistant to the Apoptotic Effects of Transforming Growth Factor-β

Blood ◽

10.1182/blood.v89.3.941 ◽

1997 ◽

Vol 89 (3) ◽

pp. 941-947 ◽

Cited By ~ 64

Author(s):

Raymond S. Douglas ◽

Renold J. Capocasale ◽

Roberta J. Lamb ◽

Peter C. Nowell ◽

Jonni S. Moore

Keyword(s):

B Cells ◽

Growth Factor ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Lymphocytic Leukemia ◽

Western World ◽

Spontaneous Apoptosis

Abstract Chronic lymphocytic leukemia (CLL) is the most common leukemia of the western world and is characterized by a slowly progressing accumulation of clonal CD5+ B cells. Our laboratory has investigated the role of transforming growth factor-β (TGF-β) and interleukin-4 (IL-4) in the pathogenesis of B-cell expansion in CLL. In vitro addition of TGF-β did not increase spontaneous apoptosis of B cells from most CLL patients, as determined using the TUNEL method, compared with a twofold increase observed in cultures of normal B cells. There was similar expression of TGF-β type II receptors on both CLL B cells and normal B cells. In contrast to apoptosis, CLL B-cell proliferation was variably inhibited with addition of TGF-β. In vitro addition of IL-4, previously reported to promote CLL B-cell survival, dramatically reduced spontaneous apoptosis of CLL B cells compared with normal B cells. CLL B-cell expression of IL-4 receptors was increased compared to normal B cells. Thus, our results show aberrant apoptotic responses of CLL B cells to TGF-β and IL-4, perhaps contributing to the relative expansion of the neoplastic clone.

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Elevation of IgE-binding factors in serum of patients with B cell- derived chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v71.1.94.94 ◽

1988 ◽

Vol 71 (1) ◽

pp. 94-98 ◽

Cited By ~ 86

Author(s):

M Sarfati ◽

D Bron ◽

L Lagneaux ◽

C Fonteyn ◽

H Frost ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

High Performance ◽

Solid Phase ◽

Intermediate Stage ◽

Lymphocytic Leukemia ◽

Serum Ige ◽

Ige Binding ◽

Ige Receptors

Abstract One hundred nineteen sera from patients with various lymphoproliferative diseases and normal sera were tested by a solid- phase radioimmunoassay (RIA) for their content in IgE-binding factor (IgE-BF), a soluble glycoprotein binding to IgE and derived from low- affinity IgE receptors (Fc epsilon R). Fc epsilon R, recently identified as CD23, are known to be expressed on the surface of B cells at the intermediate stage of differentiation. The results indicate that in all cases of chronic lymphocytic leukemia (CLL) tested (n = 40), IgE- BF levels (45 to 8,656 U/mL) were 3-fold to 500-fold higher than in 24 controls (15.5 +/- 2 U/mL). With a few exceptions, serum IgE-BF levels could differentiate patients with CLL from those with other leukemias or lymphomas. In vitro studies indicated that B lymphocytes isolated from CLL patients produced 8 to 50 times more IgE-BF than did normal B cells (P less than 0.001). IgE-BF level was correlated with the Rai stage of the disease (P = 0.002) and the lymphocyte count (P = 0.041). IgE-BF was purified to homogeneity from one CLL serum sample by a combination of affinity chromatography and reverse-phase high- performance liquid chromatography (HPLC). this IgE-BF proved identical to IgE-BF isolated from the culture supernatant of RPMI 8866 cells, a B lymphoblastoid cell line bearing Fc epsilon R and secreting IgE-BF. Indeed, the two molecules had the same mol wt (25 to 27 kd), the same isoelectric point, and the same tryptic map. We suggest that determination of serum IgE-BF might prove useful for clinical monitoring of CLL.

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Lactic dehydrogenase in normal and leukemia lymphocyte subpopulations: evidence for the presence of abnormal T cells and B cells in chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v57.2.324.324 ◽

1981 ◽

Vol 57 (2) ◽

pp. 324-327 ◽

Cited By ~ 14

Author(s):

P Rambotti ◽

S Davis

Keyword(s):

T Cells ◽

B Cells ◽

Chronic Lymphocytic Leukemia ◽

T Lymphocytes ◽

B Lymphocytes ◽

Lactic Dehydrogenase ◽

Isozyme Pattern ◽

Lymphocyte Subpopulations ◽

Lymphocytic Leukemia ◽

Ldh Activity

Abstract Lactic dehydrogenase (LDH) was quantitated and the isozyme pattern studied in lymphocyte subpopulations from normal people and patients with chronic lymphocytic leukemia (CLL). Normal T lymphocytes differed from normal B lymphocytes in having greater total LDH activity (597.2 versus 252.1). Total LDH activity in CLL T cells (347.1) was lower than normal T cells., but not significantly different than normal B cells. Total LDH activity in CLL B cells (124.6) was lower then normal B cells and normal T cells. The isozyme pattern of normal T lymphocytes showed a higher activity in the LDH-1 band (26.7% versus 5.4%) but showed a lower activity in LDH-5 band (4.3% versus 16.3%) compared to normal B cells. Chronic lymphocytic leukemia T cells could be distinguished from CLL B cells by a high LDH-5 band (22.3% versus 7.6%) and from normal T cells by a high LDH-5 band (22.3% versus 4.3%) and a low LDH-1 band (7.3% versus 26.7%). CLL B cells could be distinguished from normal B cells by a low LDH-5 band (7.6% versus 16.3%). Thus, the LDH isozyme pattern distinguishes normal T lymphocytes from normal B lymphocytes, and normal T and B lymphocytes from CLL T and B lymphocytes.

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Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic lymphocytic leukemia B cells from in vitro apoptosis

Blood ◽

10.1182/blood.v87.3.1022.bloodjournal8731022 ◽

1996 ◽

Vol 87 (3) ◽

pp. 1022-1029 ◽

Cited By ~ 56

Author(s):

N Chaouchi ◽

C Wallon ◽

C Goujard ◽

G Tertian ◽

A Rudent ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

Interleukin 2 ◽

Intermediate Stage ◽

Lymphocytic Leukemia ◽

Spontaneous Apoptosis ◽

Interleukin 13 ◽

B Cell Maturation ◽

Cd23 Expression

Human interleukin-13 (IL-13) acts at different stages of the normal B- cell maturation pathway with a spectrum of biologic activities overlapping those of IL-4. B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells, arrested at the intermediate stage of their differentiation. In vitro, B-CLL cells exhibit a spontaneous apoptosis regulated by different cytokines. In this report, we show that IL-13 (10 to 200 ng/mL) acts directly on monoclonal B-CLL cells from 12 patients. (1) IL-13 enhances CD23 expression and induces soluble CD23 secretion by B-CLL cells but does not exhibit a growth factor activity. (2) IL-13 inhibits IL-2 responsiveness of B-CLL cells, activated either with IL-2 alone or through crosslinking of lgs or ligation of CD40 antigen. (3) IL-13 protects B-CLL cells from in vitro spontaneous apoptosis. The effects of IL-13 on neoplasic B cells were slightly less than those of IL-4 and occurred independently of the presence of IL-4. The present observations show that IL-13 may exhibit a negative regulatory effect on neoplasic B cells in contrast with that observed in normal B cells, and suggest that IL-13 could be an important factor in the pathogenesis of CLL by preventing the death of monoclonal B cells. Moreover, B-CLL may be an interesting model to study the regulation of the expression of IL-13 receptor and/or signal transduction pathways.

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