Clinical Significance of CD21 Co-Expressed with LFA-1 in Non-Hodgkin’s B-Cell Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1781-1781
Author(s):  
Kazushi Tanimoto ◽  
Yoshihiro Yakushijin ◽  
Hiroshi Fujiwara ◽  
Masaki Otsuka ◽  
Koichi Ohshima ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Clinical Significance ◽  
Peritoneal Cavity ◽  
Cell Lymphoma ◽  
Biological Significance ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Hodgkin's Lymphoma ◽  
Lymphoma Cells

Abstract Since non-Hodgkin’s lymphoma is a disease of heterogeneous lymphoid malignancies, precise classification is essential for predicting the prognosis and determining the appropriate treatment strategy. Although the recent studies of gene expression profiling-based classification have successfully discriminated diffuse large B-cell lymphoma (DLBCL) into two subgroups based on the origin of lymphoma cells and their prognosis, this method is hardly applicable for the routine practice due to complexity of techniques. Because the immunohistochemistry-based classification of non-Hodgkin’s lymphoma can be easily applicable, it has been widely used in daily practice. We previously reported the favorable prognostic value of CD21 for DLBCL (Br J Haematol.2004;127:416–424). Although the research for function of CD21 in normal B lymphocytes has been progressed, little is known about the biological significance of CD21 in progression of B-cell lymphoma (BCL) line cells. Based on these backgrounds, we attempted to clarify the biological characteristics of CD21 in BCL and to determine the clinical significance of CD21 expression focusing on the mechanisms of progression and dissemination of BCL cells. To examine the characteristic changes in lymphoma cells induced by CD21 expression, CD21 gene was transfected in CD21-negative lymphoma cell line, Namalwa. The characteristics of CD21 gene-transfected B-cell lymphoma cell lines (CD21-transfectants) were compared to those of a parent CD21-negative cell line. Established clones of CD21-transfectants showed homotypic aggregation in suspension culture. Analysis of integrin expression revealed that LFA-1 (CD11a/CD18) appeared to be newly expressed on CD21-transfectants at a transcriptional level. The CD21-tranfectants could bind on plastic plate coated with ICAM-1, and ICAM-1 expression was detected on both CD21-transfectants and a parent BCL line. Cell aggregation was abrogated by adding an anti-LFA-1 antibody. Based on the findings obtained from experiments, biopsy samples of BCL (n=29) and BCL cells isolated from pleural or peritoneal cavity fluid (n=10) were analyzed by flow cytometry and/or immunohistochemical staining. Consequently, all cases positive for CD21 appeared to co-express LFA-1 unexceptionally, as observed in CD21-transfectants. Interestingly, all BCL cells isolated from pleural or peritoneal cavity fluid appeared to express neither CD21 nor LFA-1. Our data strongly suggest that absence of CD21 expression in BCL seems to correlate with lymphoma dissemination, which might be partially resulted from lacked interaction between CD21-related LFA-1 and ICAM-1, as shown in the figure. In summary, the present study demonstrates for the first time the biological significance of co-expression of CD21 and LFA-1 in the pathogenesis of lymphoma progression. Our data may shed light on understanding the mechanisms responsible for dissemination of lymphoma cells and further studies focusing on the association of CD21 and adhesion molecules are expected to develop the novel strategy for lymphoma treatment. Figure Figure

scholarly journals Prosurvival and Chemoprotective Effects of Tumor-Associated Macrophages Reversed By Anti-CSF-1R Monoclonal Antibody in B-Cell Lymphomas

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 498-498
Author(s):  
Anupama Gopisetty ◽  
Myriam Foglietta ◽  
Min Zhang ◽  
Zhiqiang Wang ◽  
Nathan Fowler ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
B Cell Lymphomas ◽  
Lymphoma Cells ◽  
Tumor Survival

Abstract The results of gene expression profiling (GEP) and immunohistochemical studies indicate that survival is worsened by macrophages (MΦ) in the tumor microenvironment of various B-cell lymphomas including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Tumor-associated macrophages (TAMs) are known to be different from other types of MΦ, but the effects of TAMs that worsen prognosis in B-cell lymphoma are essentially unknown, as are the mechanisms of these effects. Here, we determined the phenotype and effects of TAMs on tumor survival, proliferation, and drug resistance in B-cell lymphomas and evaluated strategies to reverse their effects. As compared to peripheral blood monocytes (Mo) from normal donors (ND), Mo from FL patients were differentiated less into M1 MΦ (defined as CD68+CD163loCD206loCD86hi) by culture with CSF-1 for 5 days followed by IFN-g + LPS for 2 days more. In contrast, Mo from FL patients and ND were differentiated similarly into M2 MΦ (defined as CD68+CD163hiCD206hiCD86lo) by culture with CSF-1 followed by IL-4. Consistent with this, MΦ gene signatures from FL tumors were more similar to previously-described signatures of M2 rather than M1 MΦ (Martinez et al, J Immunol, 2006, 177(10):7303-11). In co-culture, primary FL tumor cells and lymphoma cell lines (including RL, a transformed FL cell line; Granta 519, a mantle cell lymphoma (MCL) cell line; and Raji, a Burkitt lymphoma cell line) induced differentiation of Mo into MΦ. Differentiation could be prevented by CS4 monoclonal antibody (mAb), a fully human IgG1 anti-human CSF-1R mAb (ImClone/Eli Lilly), but not isotype control Ab. Elevated levels of CSF-1 in culture supernatants after addition of CS4 mAb and real-time PCR of tumor cells suggested secretion of CSF-1 by lymphoma cells. Spontaneous apoptosis of primary FL and MCL tumor cells, determined by Annexin V and propidium iodide staining, was significantly reduced by co-culture with ND Mo (p<0.01), whether pre-differentiated into MΦ with CSF-1 or not, but this protection could be reversed by CS4 mAb. Mo and/or pre-differentiated MΦ protected primary FL and MCL tumor cells from cytotoxic effects of doxorubicin and/or bendamustine (p<0.01), but CS4 mAb reversed this effect. To assess effects of MΦ on proliferation, lymphoma cell lines (RL, Granta 519, and Raji) were CFSE-labeled prior to co-culture with Mo and doxorubicin, and proliferation assessed by CFSE dilution by flow cytometry in the presence or absence of CS4 or isotype control mAbs. MΦ promoted proliferation of all three cell lines, but this effect could be reversed by CS4 mAb. To further understand the mechanism by which MΦ promote tumor survival and growth, we performed phosflow analysis and found increased phosphorylation of STAT3 in co-cultured lymphoma cells. Consistent with this, we observed a correlation between an 11-gene STAT3 activation signature, described by Huang et al in DLBCL tumors (J Clin Oncol, 2013, 52.8414), and a MΦ gene signature in whole genome GEP studies of 191 FL tumors (Pearson correlation co-efficient=0.396, p<0.001). In conclusion, our results suggest that Mo from FL patients are predisposed to differentiate into an M2-like MΦ state. The interaction between lymphoma cells and Mo/MΦ is reciprocal: a change in Mo (MΦ differentiation) induced by interaction with lymphoma tumor cells leads to a change in the tumor cells (promotion of survival, proliferation, and chemoresistance). More importantly, our results demonstrate that targeting TAMs using CS4, an anti-CSF-1R mAb, can be an effective strategy to overcome the adverse effects of TAMs and reverse chemoresistance. Further studies are needed to determine whether STAT3 activation contributes to the protumor effects of TAMs. This may provide novel insights into the molecular mechanisms related to TAMs and lymphoma cells and offers additional targets for therapeutic development. In the long term, strategies targeting TAMs is especially appealing, as they should be able to be combined with existing therapies including chemotherapy, other immunotherapy, and targeted therapy, potentially improving their efficacy without increasing toxicity for FL, DLBCL, and other B-cell malignancies. Disclosures No relevant conflicts of interest to declare.

Structure of the human retinoblastoma-related p107 gene and its intragenic deletion in a B-cell lymphoma cell line

Gene ◽  
2000 ◽  
Vol 251 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Koichi Ichimura ◽  
Hiroko Hanafusa ◽  
Hidetaka Takimoto ◽  
Yoichiro Ohgama ◽  
Tadaatsu Akagi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Intragenic Deletion ◽  
Human Retinoblastoma

Chimeric Anti-CD20 (IDEC-C2B8) Monoclonal Antibody Sensitizes a B Cell Lymphoma Cell Line to Cell Killing by Cytotoxic Drugs

1997 ◽  
Vol 12 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Aicha Demidem ◽  
Tammy Lam ◽  
Steve Alas ◽  
Kandasamy Hariharan ◽  
Nabil Hanna ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Cell Line ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Killing ◽  
Cytotoxic Drugs ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Anti Cd20

Establishment and characterization of a porcine B cell lymphoma cell line

2020 ◽  
Vol 390 (2) ◽  
pp. 111986
Author(s):  
Michael C. Rahe ◽  
Cheryl M.T. Dvorak ◽  
Barry Wiseman ◽  
Daniel Martin ◽  
Michael P. Murtaugh
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line

Anti-CD45 Mediated Cytolysis of Human T-Cell Lymphoma Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4637-4637
Author(s):  
Gerald G. Wulf ◽  
Anita Boehnke ◽  
Bertram Glass ◽  
Lorenz Truemper
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cytolytic Activity ◽  
T Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cells ◽  
Human T Cell

Abstract Anti-CD45 mediated cytoreduction is an effective means for T-cell depletion in rodents and humans. In man, the CD45-specific rat monoclonal antibodies YTH24 and YTH54 are IgG2b subclass, exert a predominantly complement-dependent cytolytic activity against normal T-lymphocytes, and have been safely given to patients as part of conditioning therapies for allogeneic stem cell transplantation. The efficacy of such antibodies against human lymphoma is unknown. Therefore, we evaluated the cytolytic activity of YTH24 and YTH54 by complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), as well as by direct apoptotic and antiproliferative effects, against a panel of Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) cell lines, and against primary specimens. Significant CDC activity (&gt;50% cytolysis) of the antibodies YTH54 and YTH24 was observed against three of five T-cell lymphoma lines, but against only one of nine B-cell lymphoma lines and none of four HD cell lines. The combination of YTH54 and YTH24 induced ADCC in all T-cell lymphoma cell lines and three primary leukemic T-cell lymphoma specimens, but were ineffective in B-cell lymphoma and HD cell lines.There were only minor effects of either antibody or the combination on lymphoma cell apoptosis or cell cycle arrest. In summary, anti-CD45 mediated CDC and ADCC via the antibodies YTH24 and YTH54 are primarily effective against lymphoma cells with T-cell phenotype, and may be an immunotherapeutic tool for the treatment of human T-cell lymphoma.

scholarly journals Protein arginine methyltransferase 5 represses tumor suppressor miRNAs that down-regulate CYCLIN D1 and c-MYC expression in aggressive B-cell lymphoma

2019 ◽  
Vol 295 (5) ◽  
pp. 1165-1180 ◽  
Author(s):  
Vrajesh Karkhanis ◽  
Lapo Alinari ◽  
Hatice Gulcin Ozer ◽  
Jihyun Chung ◽  
Xiaoli Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
Cyclin D1 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cells ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Hodgkin's Lymphomas ◽  
Protein Arginine Methyltransferase 5

Protein arginine methyltransferase-5 (PRMT5) is overexpressed in aggressive B-cell non-Hodgkin's lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma, and supports constitutive expression of CYCLIN D1 and c-MYC. Here, we combined ChIP analysis with next-generation sequencing to identify microRNA (miRNA) genes that are targeted by PRMT5 in aggressive lymphoma cell lines. We identified enrichment of histone 3 dimethylation at Arg-8 (H3(Me2)R8) in the promoter regions of miR33b, miR96, and miR503. PRMT5 knockdown de-repressed transcription of all three miRNAs, accompanied by loss of recruitment of epigenetic repressor complexes containing PRMT5 and either histone deacetylase 2 (HDAC2) or HDAC3, enhanced binding of co-activator complexes containing p300 or CREB-binding protein (CBP), and increased acetylation of specific histones, including H2BK12, H3K9, H3K14, and H4K8 at the miRNA promoters. Re-expression of individual miRNAs in B-cell lymphoma cells down-regulated expression of PRMT5, CYCLIN D1, and c-MYC, which are all predicted targets of these miRNAs, and reduced lymphoma cell survival. Luciferase reporter assays with WT and mutant 3′UTRs of CYCLIN D1 and c-MYC mRNAs revealed that binding sites for miR33b, miR96, and miR503 are critical for translational regulation of the transcripts of these two genes. Our findings link altered PRMT5 expression to transcriptional silencing of tumor-suppressing miRNAs in lymphoma cells and reinforce PRMT5's relevance for promoting lymphoma cell growth and survival.

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