scholarly journals Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10 [see comments]

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1289-1298 ◽  
Author(s):  
D Benjamin ◽  
TJ Knobloch ◽  
MA Dayton
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Northern Blot Analysis ◽  
Burkitt’S Lymphoma ◽  
Interleukin 10 ◽  
Burkitt's Lymphoma ◽  
Rt Pcr ◽  
B Cell Lymphomas ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV- positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV- negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV- positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.

scholarly journals Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10 [see comments]

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1289-1298 ◽  
Author(s):  
D Benjamin ◽  
TJ Knobloch ◽  
MA Dayton
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Northern Blot Analysis ◽  
Burkitt’S Lymphoma ◽  
Interleukin 10 ◽  
Burkitt's Lymphoma ◽  
Rt Pcr ◽  
B Cell Lymphomas ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Abstract A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV- positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV- negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV- positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.

Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma [see comments]

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3423-3430 ◽  
Author(s):  
R Masood ◽  
Y Zhang ◽  
MW Bond ◽  
DT Scadden ◽  
T Moudgil ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Antisense Oligonucleotide ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Interleukin 10 ◽  
Autocrine Growth ◽  
Autocrine Growth Factor ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL-10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombinant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL-10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis.

Modulation of Caspase-8 and FLICE-Inhibitory Protein Expression as a Potential Mechanism of Epstein-Barr Virus Tumorigenesis in Burkitt’s Lymphoma

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1727-1737 ◽  
Author(s):  
Clifford G. Tepper ◽  
Michael F. Seldin
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Pcr Analysis ◽  
Caspase 8 ◽  
Rt Pcr ◽  
Inhibitory Protein ◽  
Barr Virus ◽  
Epstein Barr

Abstract Ligation of the Fas receptor induces death-inducing signaling complex (DISC) formation, caspase activation, and subsequent apoptotic death of several cell types. Epstein-Barr virus (EBV)-positive group III Burkitt’s lymphoma (BL) cell lines have a marked resistance to Fas-mediated apoptosis, although expressing each of the DISC components, Fas/ APO-1–associated death domain protein (FADD), and caspase-8 (FLICE/MACH/Mch5). The apoptotic pathway distal to the DISC is intact because ceramide analogs, staurosporine, and granzyme B activate caspase-3 and induce apoptosis. Fas resistance was not explained by the putative death-attenuating caspase-8 isoforms. However, while Fas-activated cytosolic extracts from sensitive cells were capable of processing both procaspase-8 and procaspase-3 into active subunit forms, resistant cell extracts did not possess either of these activities. Accordingly, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed higher transcript levels for the FLICE-inhibitory protein (FLIPL) in resistant cells and the ratio of caspase-8 to FLIPLmeasured by competition RT-PCR analysis directly correlated with susceptibility to Fas-mediated apoptosis of all cell lines. In addition, modification of the caspase-8/FLIPL ratio by caspase-8 or FLIPL overexpression was able to alter the susceptibility status of the cell lines tested. Our results imply that the relative levels of caspase-8 and FLIPL are an important determinant of susceptibility to Fas-mediated apoptosis.

Effective treatment of aggressive B-cell lymphomas by downregulated NIK-induced noncanonical NF-κB pathway activation through inhibition of BAFF.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13554-e13554
Author(s):  
Sung Hsin Kuo ◽  
Li-Tzong Chen ◽  
Kun-Huei Yeh ◽  
Hui-Jen Tsai ◽  
Hsiao-Wei Lee ◽  
...  
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Nuclear Translocation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Luciferase Assay ◽  
Aggressive B Cell Lymphoma

e13554 Background: We recently reported that autocrine BAFF (B cell–activating factor belonging to the TNF family) signal transduction pathway contributes to H. pylori-independent growth of gastric diffuse large B-cell lymphoma (DLBCL) (Blood 2008;112:2927-34; Ann Hematol 2010;89:431-6). In this study, we sought to investigate whether activation of BAFF signaling pathway can promote the survival and proliferation of aggressive B-cell lymphoma. Methods: Seven aggressive NHL cell lines (EBV-negative Burkitt’s lymphoma (Ramos), EBV-positive Burkitt’s lymphoma (Raji), EBV-negative undifferentiated lymphoma (MC116), activated B cell (ABC)-like DLBCL (OCI-Ly3, OCI-Ly10), and germinal center B cell (GCB)-like DLBCL (OCI-Ly7, and Pfeiffer) were used in this study. Cell cycle was analyzed by flow cytometry. The DNA-binding activity of NF-kB was determined by the luciferase assay. Expression of non-canonical NF-κB signatures-related proteins (BAFF, BAFF-R, NIK, cIAP1, TRAF2, cIAP1/2, TRAF3, IKKa, p100, p52 and RelB, BCL10, BCL3, and STAT3) was assessed by immunoblotting. Results: Our results showed that in GCB-DLBCL cell lines, activation of BAFF induced recruitment and degradation of TRAF3, which resulted in NIK kinase accumulation, BCL10 Ser138 phosphorylation, IKKa phosphorylation, and NF-kB p100 processing, thereby resulting in continuous activation of non-canonical NF-kB pathway. This phenomenon also resulted in BCL3 nuclear translocation and STAT3 activation, and subsequently activated STAT3 downstream-regulated genes (BCL2, survivin, and cyclin D1). Furthermore, we found that inhibition of BAFF by short hairpin RNA (shRNA) suppressed the growth of ABC-DLBCL cells and Burkitt lymphoma cells through the down-regulation of BAFF/BAFF-R/TRAF3/NIK/BCL3/NF-kB signaling pathway. Conclusions: Our results indicate that constitutive BAFF signaling activates NIK-induced non-canonical NF-kB signaling pathway in aggressive B-cell lymphoma, and inhibition of BAFF is particularly effective in the treatment of this subgroup of tumors.

Novel Nanoparticle-Based Approaches To Target B-Cell Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4903-4903
Author(s):  
James A. Weaver ◽  
Candice Brannen ◽  
Joseph DeSimone ◽  
Robert Z. Orlowski
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Malignant Cell ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
B Cell Malignancies ◽  
Lymphoma Cells ◽  
Cell Clones ◽  
Systemic Treatments ◽  
Burkitt’S Lymphoma Cells

Abstract Introduction: Current approaches to the management of B-cell malignancies include the use of systemic treatments with cytotoxic chemotherapeutics that are not targeted to the tumor cell itself. By improving the ability to deliver lethal agents to the malignant cell clone, such as by targeting the unique tumor idiotype, it is possible that the therapeutic index of our current armamentarium could be improved, thereby optimizing patient outcomes. Nanoparticles represent one attractive approach in this area, since their high surface to volume ratio provides a strong driving force for diffusion into the tumor microenvironment. Methods: Studies were performed using Ramos and SUP-B8 human Burkitt’s lymphoma cell lines, as well as cell lines representative of other hematologic malignancies. Commercially available nanoparticles (Qdots; Invitrogen) as well as nanoparticles generated using PRINT (particle replication in non-wetting templates) technology, were used with idiotype and control peptides. Results: A biotinylated peptide recognized by the SUP-B8 idiotype was bound to streptavidin-containing Qdots, as well as to 200 nm polymeric PRINT particles. Both of these nanoparticle types bound specifically to SUP-B8 Burkitt’s lymphoma cells, as determined by the induction of a fluourescence shift by flow cytometry. These same particles showed no detectable binding to Ramos Burkitt’s lymphoma cells, whose idiotype recognizes a distinct set of peptide sequences, nor to other malignant cell lines, such as RPMI 8226 and ANBL-6 multiple myeloma cells. Moreover, when these nanoparticles were coated with control biotinylated peptides, no binding was seen to any of these cell types, demonstrating the specificity of this approach. Studies utilizing a number of techniques, including fluorescence and electron microscopy, revealed that, after binding, these idiotype-specific particles were internalized by SUP-B8 cells, but not by control cells, or when control peptides were used. Studies in vivo are underway to determine if these targeted nanoparticles can be used for imaging, as well as for delivery of lethal cargoes such as doxorubicin. Conclusion: Nanoparticles can be targeted to specific neoplastic B-cell clones through the use of peptides recognized by the surface idiotype, possibly thereby sparing toxic effects to other B-cell clones, as well as to non-lymphoid cells. The ability to generate nanoparticles of various chemistries, sizes, and porosity, as well as nanoparticles containing a wide array of cargoes, will allow these to be used as platforms for the future personalization of therapy of B-cell malignancies.

Isolation of the Human Interleukin 10 Promoter. Characterization of the Promoter Activity in Burkitt's Lymphoma Cell Lines

Cytokine ◽  
1995 ◽  
Vol 7 (1) ◽  
pp. 1-7 ◽  
Author(s):  
D. Kube ◽  
C. Platzer ◽  
A. von Knethen ◽  
H. Straub ◽  
H. Bohlen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Promoter Activity ◽  
Burkitt’S Lymphoma ◽  
Interleukin 10 ◽  
Lymphoma Cell ◽  
Burkitt's Lymphoma ◽  
Promoter Characterization
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