| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Institut National de la Santé et de la Recherche Médicale Unité 404, "Immunité et Vaccination," Lyon, France; and
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
The Fas/Fas ligand (L) system plays an important role in the maintenance of peripheral B cell tolerance and the prevention of misguided T cell help. CD40-derived signals are required to induce Fas expression on virgin B cells and to promote their susceptibility to Fas-mediated apoptosis. In the current study, we have analyzed the early biochemical events occurring upon Fas ligation in CD40L-activated primary human tonsillar B cells with respect to Fas-associated death domain protein (FADD), caspase-8/FADD-like IL-1ß-converting enzyme (FLICE), and c-FLICE inhibitory protein (FLIP). We report here that Fas-induced apoptosis in B cells does not require integrity of the mitochondrial Apaf-1 pathway and that caspase-8 is activated by association with the death-inducing signaling complex (DISC), i.e., upstream of the mitochondria. We show that both FADD and the zymogen form of caspase-8 are constitutively expressed at high levels in virgin B cells, whereas c-FLIP expression is marginal. In contrast, c-FLIP, but neither FADD nor procaspase-8, is strongly up-regulated upon ligation of CD40 or the B cell receptor on virgin B cells. Finally, we have found that c-FLIP is also recruited and cleaved at the level of the DISC in CD40L-activated virgin B cells. We propose that c-FLIP expression delays the onset of apoptosis in Fas-sensitive B cells. The transient protection afforded by c-FLIP could offer an ultimate safeguard mechanism against inappropriate cell death or allow recruitment of phagocytes to ensure efficient removal of apoptotic cells.
This article has been cited by other articles:
|
|
 |
|
  N. Ueffing, K. K. Singh, A. Christians, C. Thorns, A. C. Feller, F. Nagl, F. Fend, S. Heikaus, A. Marx, R. B. Zotz, et al. A single nucleotide polymorphism determines protein isoform production of the human c-FLIP protein Blood, July 16, 2009; 114(3): 572 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Troeger, I. Schmitz, M. Siepermann, L. Glouchkova, U. Gerdemann, G. E. Janka-Schaub, K. Schulze-Osthoff, and D. Dilloo Up-regulation of c-FLIPS+R upon CD40 stimulation is associated with inhibition of CD95-induced apoptosis in primary precursor B-ALL Blood, July 1, 2007; 110(1): 384 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, S. Wang, H. Maeng, D. P. Young, O. Prakash, L. E. Fayad, A. Younes, and F. Samaniego K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis Blood, March 1, 2007; 109(5): 2174 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Barrington, M. Zhang, X. Zhong, H. Jonsson, N. Holodick, A. Cherukuri, S. K. Pierce, T. L. Rothstein, and M. C. Carroll CD21/CD19 Coreceptor Signaling Promotes B Cell Survival during Primary Immune Responses J. Immunol., September 1, 2005; 175(5): 2859 - 2867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. F. Muris, S. A. G. M. Cillessen, W. Vos, I. S. van Houdt, J. A. Kummer, J. H. J. M. van Krieken, N. M. Jiwa, P. M. Jansen, H. C. Kluin-Nelemans, G. J. Ossenkoppele, et al. Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas Blood, April 1, 2005; 105(7): 2916 - 2923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mezzanzanica, E. Balladore, F. Turatti, E. Luison, P. Alberti, M. Bagnoli, M. Figini, A. Mazzoni, F. Raspagliesi, M. Oggionni, et al. CD95-Mediated Apoptosis Is Impaired at Receptor Level by Cellular FLICE-Inhibitory Protein (Long Form) in Wild-Type p53 Human Ovarian Carcinoma Clin. Cancer Res., August 1, 2004; 10(15): 5202 - 5214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dutton, J. D. O'Neil, A. E. Milner, G. M. Reynolds, J. Starczynski, J. Crocker, L. S. Young, and P. G. Murray Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin's lymphoma cells from autonomous Fas-mediated death PNAS, April 27, 2004; 101(17): 6611 - 6616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kern, J.-F. Cornuel, C. Billard, R. Tang, D. Rouillard, V. Stenou, T. Defrance, F. Ajchenbaum-Cymbalista, P.-Y. Simonin, S. Feldblum, et al. Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway Blood, January 15, 2004; 103(2): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. A. Mongini, A. E. Jackson, S. Tolani, R. J. Fattah, and J. K. Inman Role of Complement-Binding CD21/CD19/CD81 in Enhancing Human B Cell Protection from Fas-Mediated Apoptosis J. Immunol., November 15, 2003; 171(10): 5244 - 5254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zazzeroni, S. Papa, A. Algeciras-Schimnich, K. Alvarez, T. Melis, C. Bubici, N. Majewski, N. Hay, E. De Smaele, M. E. Peter, et al. Gadd45{beta} mediates the protective effects of CD40 costimulation against Fas-induced apoptosis Blood, November 1, 2003; 102(9): 3270 - 3279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Schmitz, A. Krueger, S. Baumann, H. Schulze-Bergkamen, P. H. Krammer, and S. Kirchhoff An IL-2-Dependent Switch Between CD95 Signaling Pathways Sensitizes Primary Human T Cells Toward CD95-Mediated Activation-Induced Cell Death J. Immunol., September 15, 2003; 171(6): 2930 - 2936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fukui, R. Imamura, M. Umemura, T. Kawabe, and T. Suda Pathogen-Associated Molecular Patterns Sensitize Macrophages to Fas Ligand-Induced Apoptosis and IL-1{beta} Release J. Immunol., August 15, 2003; 171(4): 1868 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Maggio, A. van den Berg, D. de Jong, A. Diepstra, and S. Poppema Low Frequency of FAS Mutations in Reed-Sternberg Cells of Hodgkin's Lymphoma Am. J. Pathol., January 1, 2003; 162(1): 29 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Leoncini, S Lazzi, C Bellan, and P Tosi Cell kinetics and cell cycle regulation in lymphomas J. Clin. Pathol., September 1, 2002; 55(9): 648 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Thomas, A. Kallenborn, C. Wickenhauser, J. L. Schultze, A. Draube, M. Vockerodt, D. Re, V. Diehl, and J. Wolf Constitutive Expression of c-FLIP in Hodgkin and Reed-Sternberg Cells Am. J. Pathol., April 1, 2002; 160(4): 1521 - 1528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chu, D. Deforce, I. M. Pedersen, Y. Kim, S. Kitada, J. C. Reed, and T. J. Kipps Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia PNAS, March 19, 2002; 99(6): 3854 - 3859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Maianski, F. P. J. Mul, J. D. van Buul, D. Roos, and T. W. Kuijpers Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils Blood, January 15, 2002; 99(2): 672 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Krueger, S. Baumann, P. H. Krammer, and S. Kirchhoff FLICE-Inhibitory Proteins: Regulators of Death Receptor-Mediated Apoptosis Mol. Cell. Biol., December 15, 2001; 21(24): 8247 - 8254. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Owyang, J. R. Tumang, B. R. Schram, C. Y. Hsia, T. W. Behrens, T. L. Rothstein, and H.-C. Liou c-Rel Is Required for the Protection of B Cells from Antigen Receptor-Mediated, But Not Fas-Mediated, Apoptosis J. Immunol., November 1, 2001; 167(9): 4948 - 4956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Snow, L. J. Chen, R. R. Nepomuceno, S. M. Krams, C. O. Esquivel, and O. M. Martinez Resistance to Fas-Mediated Apoptosis in EBV-Infected B Cell Lymphomas Is Due to Defects in the Proximal Fas Signaling Pathway J. Immunol., November 1, 2001; 167(9): 5404 - 5411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. van Eijk, J. P. Medema, and C. de Groot Cutting Edge: Cellular Fas-Associated Death Domain-Like IL-1-Converting Enzyme-Inhibitory Protein Protects Germinal Center B Cells from Apoptosis During Germinal Center Reactions J. Immunol., June 1, 2001; 166(11): 6473 - 6476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hennino, M. Berard, P. H. Krammer, and T. Defrance FLICE-inhibitory Protein Is a Key Regulator of Germinal Center B Cell Apoptosis J. Exp. Med., February 12, 2001; 193(4): 447 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Krueger, I. Schmitz, S. Baumann, P. H. Krammer, and S. Kirchhoff Cellular FLICE-inhibitory Protein Splice Variants Inhibit Different Steps of Caspase-8 Activation at the CD95 Death-inducing Signaling Complex J. Biol. Chem., June 1, 2001; 276(23): 20633 - 20640. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
