scholarly journals IgE synthesis by chronic lymphocytic leukemia cells.

1989 ◽  
Vol 170 (5) ◽  
pp. 1775-1780 ◽  
Author(s):  
M Sarfati ◽  
H Luo ◽  
G Delespesse
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Fluorescence Staining ◽  
Immunological Parameters ◽  
Potent Inducer ◽  
Human B Cells ◽  
Ige Synthesis ◽  
Cd23 Expression ◽  
Chain Type

The present results indicate that B cells isolated from chronic lymphocytic leukemia (B-CLL) from 11 of 14 patients are capable of specifically producing IgE upon costimulation with IL-4 and hydrocortisone (HC). IgE is detected by intracytoplasmic fluorescence staining and by RIA. Clinical, hematological, and immunological parameters (including Rai stage, WBC, Lc, sIg kappa/lambda, CD5, and CD23 expression) cannot distinguish the IgE responder from the nonresponder patients. IL-4 alone is a potent inducer of human IgE synthesis by normal PBMC and we show here that its effect is strikingly enhanced by HC. The IgE produced by B-CLLs are monoclonal since they display the same L chain type as the freshly isolated CD5+ B-CLLs. We, therefore, conclude that the combination of IL-4 and HC can abrogate the maturation arrest of CD5+ B-CLLs by inducing their differentiation into IgE-producing cells. The present data provide a unique model to study the isotype switching to IgE and the regulation of human IgE synthesis by monoclonal human B cells.

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

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 1022-1029 ◽  
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.

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

1989 ◽  
Vol 169 (1) ◽  
pp. 255-268 ◽  
Author(s):  
Z M Sthoeger ◽  
M Wakai ◽  
D B Tse ◽  
V P Vinciguerra ◽  
S L Allen ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Autoimmune Disorders ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Antigenic Specificity ◽  
Human B Cells ◽  
Well Differentiated

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.

scholarly journals Immunoglobulin phenotype on B cells correlates with clinical stage of chronic lymphocytic leukemia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 256-263
Author(s):  
FS Ligler ◽  
JR Kettman ◽  
RG Smith ◽  
EP Frenkel
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Clinical Stage ◽  
Lymphocytic Leukemia ◽  
Light Chain Type ◽  
Immature B Cells ◽  
Advanced Stages ◽  
Ig Heavy Chain ◽  
Chain Type

The present study examines the relative amounts of surface immunoglobulin (Ig) on lymphocytes obtained from 64 patients with chronic lymphocytic leukemia (CLL) and correlates these findings with the clinical stage of disease. Since the maturing B cell first expresses surface IgM, followed by IgD, and subsequently by IgG, IgA, or IgE, the surface Ig phenotype can be used as a marker of differentiation. Surface Ig was analyzed using the fluorescence- activated cell sorter under carefully controlled conditions. The cells from all patients with CLL were monoclonal with respect to light chain type. Those patients with IgM as the brightest heavy chain class (suggesting relatively immature B cells) had clinically advanced stages of CLL, whereas those with a predominance of IgG (suggesting more mature cells) have a lesser stage of CLL. Thus, the predominant Ig heavy chain class appears to correlate with clinical stage of CLL and provides a clue to the potential aggressiveness of the tumor.

scholarly journals Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells.

1993 ◽  
Vol 90 (8) ◽  
pp. 3730-3734 ◽  
Author(s):  
J. Punnonen ◽  
G. Aversa ◽  
B. G. Cocks ◽  
A. N. McKenzie ◽  
S. Menon ◽  
...  
Keyword(s):  
B Cells ◽  
Interleukin 4 ◽  
Interleukin 13 ◽  
Human B Cells ◽  
Ige Synthesis ◽  
Cd23 Expression

scholarly journals Immunoglobulin phenotype on B cells correlates with clinical stage of chronic lymphocytic leukemia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 256-263 ◽  
Author(s):  
FS Ligler ◽  
JR Kettman ◽  
RG Smith ◽  
EP Frenkel
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Clinical Stage ◽  
Lymphocytic Leukemia ◽  
Light Chain Type ◽  
Immature B Cells ◽  
Advanced Stages ◽  
Ig Heavy Chain ◽  
Chain Type

Abstract The present study examines the relative amounts of surface immunoglobulin (Ig) on lymphocytes obtained from 64 patients with chronic lymphocytic leukemia (CLL) and correlates these findings with the clinical stage of disease. Since the maturing B cell first expresses surface IgM, followed by IgD, and subsequently by IgG, IgA, or IgE, the surface Ig phenotype can be used as a marker of differentiation. Surface Ig was analyzed using the fluorescence- activated cell sorter under carefully controlled conditions. The cells from all patients with CLL were monoclonal with respect to light chain type. Those patients with IgM as the brightest heavy chain class (suggesting relatively immature B cells) had clinically advanced stages of CLL, whereas those with a predominance of IgG (suggesting more mature cells) have a lesser stage of CLL. Thus, the predominant Ig heavy chain class appears to correlate with clinical stage of CLL and provides a clue to the potential aggressiveness of the tumor.

THE ROLE OF THE GENETIC ABNORMALITIES, EPIGENETIC AND microRNA IN THE PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA

2018 ◽  
Vol 40 (4) ◽  
pp. 261-267 ◽  
Author(s):  
K Tari ◽  
Z Shamsi ◽  
H Reza Ghafari ◽  
A Atashi ◽  
M Shahjahani ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
P53 Mutation ◽  
Lymphocytic Leukemia ◽  
Gene Promoters ◽  
Epigenetic Changes ◽  
Genetic Changes ◽  
Trisomy 12

Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood and bone marrow involvement, which is usually observed in older people. Genetic mutations, epigenetic changes and miRs play a role in CLL pathogenesis. Del 11q, del l17q, del 6q, trisomy 12, p53 and IgVH mutations are the most important genetic changes in CLL. Deletion of miR-15a and miR-16a can increase bcl2 gene expression, miR-29 and miR-181 deletions decrease the expression of TCL1, and miR-146a deletion prevents tumor metastasis. Epigenetic changes such as hypo- and hypermethylation, ubiquitination, hypo- and hyperacetylation of gene promoters involved in CLL pathogenesis can also play a role in CLL. Expression of CD38 and ZAP70, presence or absence of mutation in IgVH and P53 mutation are among the factors involved in CLL prognosis. Use of monoclonal antibodies against surface markers of B-cells like anti-CD20 as well as tyrosine kinase inhibitors are the most important therapeutic approaches for CLL.

scholarly journals Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

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.

STAT6 and the regulation of CD23 expression in B-chronic lymphocytic leukemia

2000 ◽  
Vol 24 (4) ◽  
pp. 331-337 ◽  
Author(s):  
C. Kneitz ◽  
M. Goller ◽  
R. Seggewiss ◽  
A. Yaman ◽  
E. Serfling ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Cd23 Expression

scholarly journals Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome)

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 45-50 ◽  
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
M Mayumi ◽  
JT Prchal ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Plasma Cells ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Immunoglobulin Gene ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Richter’S Syndrome

Abstract A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly “frozen” in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.

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