Modulation of Macrophage Inflammatory Protein-1α and Its Receptors in Human B-Cell Lines Derived from Patients with Acquired Immunodeficiency Syndrome and Burkitt's Lymphoma

1997 ◽  
Vol 235 (3) ◽  
pp. 576-581 ◽  
Author(s):  
Venkatanarayanan Sharma ◽  
Daniel Walper ◽  
Richard Deckert
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Acquired Immunodeficiency Syndrome ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Inflammatory Protein ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Macrophage Inflammatory Protein ◽  
Human B Cell

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.

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 Abnormal Expression of the B-Cell Homing Chemokine Receptor BLR1 During the Progression of Acquired Immunodeficiency Syndrome

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 520-525 ◽  
Author(s):  
Reinhold Förster ◽  
Georgina Schweigard ◽  
Sabine Johann ◽  
Thomas Emrich ◽  
Elisabeth Kremmer ◽  
...  
Keyword(s):  
B Cell ◽  
Chemokine Receptor ◽  
Acquired Immunodeficiency Syndrome ◽  
Peripheral Blood ◽  
Lymphoid Tissue ◽  
Healthy Individuals ◽  
T Helper ◽  
Cell Homing ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Abstract The putative chemokine receptor BLR1 has been identified as the first G-protein–coupled receptor involved in B-cell migration and in microenvironmental homing to B-cell follicles and to germinal centers. In healthy individuals, expression of BLR1 is restricted to all mature recirculating B cells and to a subpopulation of T-helper memory cells. In the present study, we analyzed the distribution of BLR1 on defined lymphocyte subsets during the progression of acquired immunodeficiency syndrome. It is shown that the proportion of T-helper memory cells coexpressing BLR1 continuously decreases during the infection, whereas a high proportion of γ/δ T cells expressing BLR1 can be found in peripheral blood. The latter subpopulation is restricted to lymphoid tissues in healthy individuals. Most interestingly, in 75% of all human immunodeficiency virus (HIV)+ individuals, peripheral blood B cells were identified as not expressing BLR1 and phenotypically resembling germinal center cells of lymphoid tissue. Using BLR1 as a marker molecule, this study identifies peripheral blood lymphocytes in HIV+ individuals that are usually restricted to lymphoid tissue in healthy individuals. Because HIV infection is active in lymphoid tissue even at the clinically latent stage, aberrant expression of the B-cell homing chemokine receptor BLR1 might be an early indicator for the onset of destruction of lymphoid tissue.

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.

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