The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     
 


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lens, S. M. A.
Right arrow Articles by van Lier, R. A. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lens, S. M. A.
Right arrow Articles by van Lier, R. A. W.
The Journal of Immunology, 1998, 160: 6083-6092.
Copyright © 1998 by The American Association of Immunologists

Dissection of Pathways Leading to Antigen Receptor-Induced and Fas/CD95-Induced Apoptosis in Human B Cells1

Susanne M. A. Lens2,*, Bianca F. A. den Drijver*, Andy J. G. Pötgens{dagger}, Kiki Tesselaar*, Marinus H. J. van Oers{ddagger} and René A. W. van Lier*

Departments of * Clinical Viro-Immunology and {dagger} Experimental Immunohematology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, and {ddagger} Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands

To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma cell line Ramos with different apoptosis sensitivities. Selection for sensitivity to Fas-induced apoptosis also selected for clones with enhanced BCR death sensitivity and vice versa. In contrast, clones resistant to Fas-mediated apoptosis could still undergo BCR-induced cell death. Based on the functional phenotypes of these clones, we hypothesized that both receptor-induced apoptosis pathways are initially distinct but may eventually converge. Indeed, ligation of both Fas and BCR resulted in cleavage of the IL-1ß-converting enzyme/Ced-3-like protease caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and poly(ADP-ribose) polymerase. Markedly, qualitative differences in the caspase 3 cleavage pattern induced by Fas or BCR ligation were observed; whereas Fas ligation generated caspase 3 cleavage products of 19/20 and 17 kDa, only the latter cleavage product was found upon BCR cross-linking. The caspase inhibitor Val-Ala-Asp-fluoromethylketone blocked both Fas- and BCR-mediated apoptosis, but differentially affected caspase 3 cleavage induced by either stimulus. Finally, overexpression of a Fas-associated death domain (FADD) dominant-negative mutant protein was found to inhibit Fas-induced apoptosis but not BCR-induced apoptosis. Together our findings imply that Fas and BCR couple, via FADD-dependent and FADD-independent mechanisms, respectively, to distinct proteases upstream of caspase 3.




This article has been cited by other articles:


Home page
BloodHome page
A. Ruiz-Vela, M. Aggarwal, P. de la Cueva, C. Treda, B. Herreros, D. Martin-Perez, O. Dominguez, and M. A. Piris
Lentiviral (HIV)-based RNA interference screen in human B-cell receptor regulatory networks reveals MCL1-induced oncogenic pathways
Blood, February 1, 2008; 111(3): 1665 - 1676.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
L. A. Smit, D. Y.H. Hallaert, R. Spijker, B. de Goeij, A. Jaspers, A. P. Kater, M. H.J. van Oers, C. J.M. van Noesel, and E. Eldering
Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity
Blood, February 15, 2007; 109(4): 1660 - 1668.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Poggianella, M. Bestagno, and O. R. Burrone
The Extracellular Membrane-Proximal Domain of Human Membrane IgE Controls Apoptotic Signaling of the B Cell Receptor in the Mature B Cell Line A20
J. Immunol., September 15, 2006; 177(6): 3597 - 3605.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
Y. Xing, H. Igarashi, X. Wang, and N. Sakaguchi
Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor-induced apoptosis
J. Exp. Med., September 6, 2005; 202(5): 707 - 719.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
A. Enders, P. Bouillet, H. Puthalakath, Y. Xu, D. M. Tarlinton, and A. Strasser
Loss of the Pro-Apoptotic BH3-only Bcl-2 Family Member Bim Inhibits BCR Stimulation-induced Apoptosis and Deletion of Autoreactive B Cells
J. Exp. Med., October 6, 2003; 198(7): 1119 - 1126.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
C. S. Goodyear and G. J. Silverman
Death by a B Cell Superantigen: In Vivo VH-targeted Apoptotic Supraclonal B Cell Deletion by a Staphylococcal Toxin
J. Exp. Med., May 5, 2003; 197(9): 1125 - 1139.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. E. Muscarella and S. E. Bloom
Cross-linking of Surface IgM in the Burkitt's Lymphoma Cell Line ST486 Provides Protection against Arsenite- and Stress-induced Apoptosis That Is Mediated by ERK and Phosphoinositide 3-Kinase Signaling Pathways
J. Biol. Chem., January 31, 2003; 278(6): 4358 - 4367.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. Hase, Y. Kanno, H. Kojima, C. Morimoto, K. Okumura, and T. Kobata
CD27 and CD40 Inhibit p53-independent Mitochondrial Pathways in Apoptosis of B Cells Induced by B Cell Receptor Ligation
J. Biol. Chem., November 27, 2002; 277(49): 46950 - 46958.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
W. J. M. Mackus, S. M. A. Lens, R. H. Medema, M. J. Kwakkenbos, L. M. Evers, M. H. J. v. Oers, R. A. W. v. Lier, and E. Eldering
Prevention of B cell antigen receptor-induced apoptosis by ligation of CD40 occurs downstream of cell cycle regulation
Int. Immunol., September 1, 2002; 14(9): 973 - 982.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
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]


Home page
J. Immunol.Home page
H. Yoshikawa, Y. Nakajima, and K. Tasaka
IFN-{gamma} Induces the Apoptosis of WEHI 279 and Normal Pre-B Cell Lines by Expressing Direct Inhibitor of Apoptosis Protein Binding Protein with Low pI
J. Immunol., September 1, 2001; 167(5): 2487 - 2495.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
W.-K. Hofmann, S. de Vos, K. Tsukasaki, W. Wachsman, G. S. Pinkus, J. W. Said, and H. P. Koeffler
Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide microarray
Blood, August 1, 2001; 98(3): 787 - 794.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
L. Besnault, N. Schrantz, M. T. Auffredou, G. Leca, M. F. Bourgeade, and A. Vazquez
B Cell Receptor Cross-Linking Triggers a Caspase-8- Dependent Apoptotic Pathway That Is Independent of the Death Effector Domain of Fas-Associated Death Domain Protein
J. Immunol., July 15, 2001; 167(2): 733 - 740.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
M. T. Tian, C.-H. G. Chou, and A. L. DeFranco
Apoptosis induced by the antigen receptor and Fas in a variant of the immature B cell line WEHI-231 and in splenic immature B cells
Int. Immunol., April 1, 2001; 13(4): 581 - 592.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
E. Takada, H. Toyota, J. Suzuki, and J. Mizuguchi
Prevention of Anti-IgM-Induced Apoptosis Accompanying G1 Arrest in B Lymphoma Cells Overexpressing Dominant-Negative Mutant Form of c-Jun N-Terminal Kinase 1
J. Immunol., February 1, 2001; 166(3): 1641 - 1649.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
P. A. Baars, L. M. Ribeiro do Couto, J. H. W. Leusen, B. Hooibrink, T. W. Kuijpers, S. M. A. Lens, and R. A. W. van Lier
Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27- Human T Cells
J. Immunol., August 15, 2000; 165(4): 1910 - 1917.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
T. Yoshida, T. Higuchi, H. Hagiyama, A. Strasser, K. Nishioka, and T. Tsubata
Rapid B cell apoptosis induced by antigen receptor ligation does not require Fas (CD95/APO-1), the adaptor protein FADD/MORT1 or CrmA-sensitive caspases but is defective in both MRL-+/+ and MRL-lpr/lpr mice
Int. Immunol., April 1, 2000; 12(4): 517 - 526.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Berard, P. Mondiere, M. Casamayor-Palleja, A. Hennino, C. Bella, and T. Defrance
Mitochondria Connects the Antigen Receptor to Effector Caspases During B Cell Receptor-Induced Apoptosis in Normal Human B Cells
J. Immunol., November 1, 1999; 163(9): 4655 - 4662.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
W. Chen, H.-G. Wang, S. M. Srinivasula, E. S. Alnemri, and N. R. Cooper
B Cell Apoptosis Triggered by Antigen Receptor Ligation Proceeds Via a Novel Caspase-Dependent Pathway
J. Immunol., September 1, 1999; 163(5): 2483 - 2491.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
T. Doi, N. Motoyama, A. Tokunaga, and T. Watanabe
Death signals from the B cell antigen receptor target mitochondria, activating necrotic and apoptotic death cascades in a murine B cell line, WEHI-231
Int. Immunol., June 1, 1999; 11(6): 933 - 941.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. R. Karp, K. Shimooku, and P. E. Lipsky
Expression of gamma -Glutamyl Transpeptidase Protects Ramos B Cells from Oxidation-induced Cell Death
J. Biol. Chem., February 2, 2001; 276(6): 3798 - 3804.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
R. Marches, E. S. Vitetta, and J. W. Uhr
A role for intracellular pH in membrane IgM-mediated cell death of human B lymphomas
PNAS, March 13, 2001; 98(6): 3434 - 3439.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.