The prevention of spontaneous apoptosis of follicular lymphoma B cells by a follicular dendritic cell line: involvement of caspase-3, caspase-8 and c-FLIP

• Published in: Haematologica (Roma) Vol. 93; no. 8; pp. 1169 - 1177
• Main Authors: Goval, Jean-Jacques, Thielen, Caroline, Bourguignon, Caroline, Greimers, Roland, Dejardin, Emmanuel, Choi, Yong Sung, Boniver, Jacques, de Leval, Laurence
• Format: Journal Article Web Resource
• Language: English
• Published: Pavia Haematologica 01-08-2008; Ferrata Storti Foundation
• Subjects: Aged; Aged, 80 and over; Anatomie (cytologie, histologie, embryologie...) & physiologie; Anatomy (cytology, histology, embryology...) & physiology; Apoptosis; B-Lymphocytes - enzymology; B-Lymphocytes - pathology; B-Lymphocytes/enzymology/pathology; Biological and medical sciences; Biopsy; CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism; Caspase 3 - metabolism; Caspase 8 - metabolism; Cell Line, Tumor; Dendritic Cells, Follicular - enzymology; Dendritic Cells, Follicular - pathology; Dendritic Cells, Follicular/enzymology/pathology; Enzyme Activation; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Human health sciences; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life sciences; Lymphoma, Follicular - enzymology; Lymphoma, Follicular - epidemiology; Lymphoma, Follicular - genetics; Lymphoma, Follicular - pathology; Lymphoma, Follicular/enzymology/epidemiology/genetics/pathology; Male; Medical sciences; Middle Aged; Oncologie; Oncology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism; Sciences de la santé humaine; Sciences du vivant; United States - epidemiology; United States; Dendritic cell; Hematology; Enzyme; Follicular cell; Cysteine endopeptidases; Spontaneous; B cell neoplasm; Malignant hemopathy; B-Lymphocyte; Lymphoid neoplasm; Non Hodgkin lymphoma; Prevention; Peptidases; Antigen presenting cell; Cell death; Lymphoproliferative syndrome; FLIP protein; Established cell line; Follicular lymphoma; Hydrolases; follicular dendritic cells; Cancer; Apoptosis
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.12127

Department of Pathology and Groupe Interdisciplinaire de Génoprotéomique Appliqué (GIGA)- Research, CHU Sart Tilman, University of Liege, Liege, Belgium
Correspondence: Laurence de Leval, MD, PhD, Department of Pathology, CHU Sart-Tilman B23 Tour de Pathologie (+1) B-4000 Liège, Belgium. E-mail: L.deLeval{at}ulg.ac.be
Background: Follicular lymphoma, the neoplastic counterpart of germinal center B cells, typically recapitulates a follicular architecture. Several observations point to the crucial role of the cellular microenvironment in the development and/or progression of follicular lymphoma cells in vivo . The aim of our study was to characterize the spontaneous apoptosis of follicular lymphoma cells in vitro , and the modulation of this apoptosis by follicular dendritic cells.
Design and Methods: We used a cell line derived from follicular dendritic cells to model the functional interactions of these cells and lymphoma cells in co-culture. Follicular lymphoma cells were isolated from tissue biopsies. Apoptosis was quantified by flow cytometry and apoptotic pathways were investigated by western blotting.
Results: The spontaneous apoptosis of follicular lymphoma cells in vitro involves the activation of caspases-3 and -8 but not of caspase-9, occurs despite persistent high levels of BCL-2 and MCL-1, and is associated with down-regulation of c-FLIP L . Spontaneous apoptosis of follicular lymphoma cells is partially prevented by co-culture with the follicular dendritic cells, which prevents activation of caspase-8, caspase-3 and induces an upregulation of c-FLIP L . Using neutralizing antibodies, we demonstrated that interactions involving CD54 (ICAM-1), CD106 (VCAM-1) and CD40 are implicated in this biological process.
Conclusions: Follicular dendritic cells constitute a useful tool to study the functional interactions between follicular lymphoma cells and follicular dendritic cells in vitro . Understanding the molecular mechanisms involved in these protective interactions may lead to the identification of therapeutic agents that might suppress the survival and growth of follicular lymphoma cells.
Key words: follicular lymphoma, follicular dendritic cells, apoptosis.