Fas ligation induces apoptosis of CD40-activated human B lymphocytes

doi:10.1084/jem.182.5.1265

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Fas ligation induces apoptosis of CD40-activated human B lymphocytes

P Garrone, EM Neidhardt, E Garcia, L Galibert, C van Kooten and J Banchereau
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.

Since CD40/CD40 ligand (CD40Lig) interactions are essential in vivo for the generation of germinal center B cells that express Fas (Apo- 1/CD95), we explored whether CD40 engagement may modulate Fas expression and function on human B lymphocytes. Resting tonsil B cells, isolated by density gradient centrifugation, express either absent or low levels of Fas. They could be induced to promptly express Fas after ligation of their CD40, however, using either a recombinant human CD40Lig or a cross-linked anti-CD40 mAb. In contrast, engagement of the B cell antigen receptor by immobilized anti-kappa and -lambda antibodies did not turn on Fas expression. Addition of anti-Fas mAb CH11 inhibited the later phases of CD40-induced B cell growth as a result of apoptotic cell death. Furthermore, Fas ligation inhibited proliferation and Ig secretion of CD40-activated B cells in response to recombinant cytokines such as interleukin (IL)-2, IL-4, and IL-10, as well as a cytokine-rich supernatant of phytohemagglutinin-activated T cells, indicating that none of those B cell tropic factors were able to prevent the Fas-induced death. Taken together, the present results show that engagement of CD40 antigen on B cells induces Fas expression and sensitizes them to Fas-mediated apoptosis. The delayed functional response to Fas ligation after CD40 activation may represent a way to limit the size of a specific B cell clone that is generated during T-B cell interactions.
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De Milito, A., Nagy, N., Samuelsson, A., Chiodi, F., Rajnavolgyi, E. (1998). Nerve Growth Factor Released by CD40 Ligand-Transfected L Cells: Implications for Functional and Phenotypic Studies on CD40+ Cells. Blood 92: 4482-4484 [Full Text]
Tangye, S. G., Liu, Y.-J., Aversa, G., Phillips, J. H., de Vries, J. E. (1998). Identification of Functional Human Splenic Memory B Cells by Expression of CD148 and CD27. JEM 188: 1691-1703 [Abstract] [Full Text]
Voorzanger-Rousselot, N., Favrot, M.-C., Blay, J.-Y. (1998). Resistance to Cytotoxic Chemotherapy Induced by CD40 Ligand in Lymphoma Cells. Blood 92: 3381-3387 [Abstract] [Full Text]
Spets, H., Georgii-Hemming, P., Siljason, J., Nilsson, K., Jernberg-Wiklund, H. (1998). Fas/APO-1 (CD95)-Mediated Apoptosis Is Activated by Interferon-gamma and Interferon-alpha in Interleukin-6 (IL-6)-Dependent and IL-6-Independent Multiple Myeloma Cell Lines. Blood 92: 2914-2923 [Abstract] [Full Text]
Dubois, B., Massacrier, C., Vanbervliet, B., Fayette, J., Briere, F., Banchereau, J., Caux, C. (1998). Critical Role of IL-12 in Dendritic Cell-Induced Differentiation of Naive B Lymphocytes. J. Immunol. 161: 2223-2231 [Abstract] [Full Text]
Ballantyne, J., Henry, D. L., Muller, J. R., Briere, F., Snapper, C. M., Kehry, M., Marcu, K. B. (1998). Efficient Recombination of a Switch Substrate Retrovector in CD40-Activated B Lymphocytes: Implications for the Control of CH Gene Switch Recombination. J. Immunol. 161: 1336-1347 [Abstract] [Full Text]
Dieu, M.-C., Vanbervliet, B., Vicari, A., Bridon, J.-M., Oldham, E., Ait-Yahia, S., Briere, F., Zlotnik, A., Lebecque, S., Caux, C. (1998). Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites. JEM 188: 373-386 [Abstract] [Full Text]
Lens, S. M. A., den Drijver, B. F. A., Potgens, A. J. G., Tesselaar, K., van Oers, M. H. J., van Lier, R. A. W. (1998). Dissection of Pathways Leading to Antigen Receptor-Induced and Fas/CD95-Induced Apoptosis in Human B Cells. J. Immunol. 160: 6083-6092 [Abstract] [Full Text]
Stohl, W., Elliott, J. E., Lynch, D. H., Kiener, P. A. (1998). CD95 (Fas)-Based, Superantigen-Dependent, CD4+ T Cell-Mediated Down-Regulation of Human In Vitro Immunoglobulin Responses. J. Immunol. 160: 5231-5238 [Abstract] [Full Text]
Plumas, J., Jacob, M.-C., Chaperot, L., Molens, J.-P., Sotto, J.-J., Bensa, J.-C. (1998). Tumor B Cells From Non-Hodgkin's Lymphoma Are Resistant to CD95 (Fas/Apo-1)-Mediated Apoptosis. Blood 91: 2875-2885 [Abstract] [Full Text]
Foote, L. C., Marshak-Rothstein, A., Rothstein, T. L. (1998). Tolerant B Lymphocytes Acquire Resistance to Fas-mediated Apoptosis after Treatment with Interleukin 4 but Not after Treatment with Specific Antigen Unless a Surface Immunoglobulin Threshold Is Exceeded. JEM 187: 847-853 [Abstract] [Full Text]
Lewinsohn, D. M., Bement, T. T., Xu, J., Lynch, D. H., Grabstein, K. H., Reed, S. G., Alderson, M. R. (1998). Human Purified Protein Derivative-Specific CD4+ T Cells Use Both CD95-Dependent and CD95-Independent Cytolytic Mechanisms. J. Immunol. 160: 2374-2379 [Abstract] [Full Text]
de Saint-Vis, B., Fugier-Vivier, I., Massacrier, C., Gaillard, C., Vanbervliet, B., Ait-Yahia, S., Banchereau, J., Liu, Y.-J., Lebecque, S., Caux, C. (1998). The Cytokine Profile Expressed by Human Dendritic Cells Is Dependent on Cell Subtype and Mode of Activation. J. Immunol. 160: 1666-1676 [Abstract] [Full Text]
Ayala, A., Xin Xu, Y., Ayala, C. A., Sonefeld, D. E., Karr, S. M., Evans, T. A., Chaudry, I. H. (1998). Increased Mucosal B-Lymphocyte Apoptosis During Polymicrobial Sepsis Is a Fas Ligand But Not an Endotoxin-Mediated Process. Blood 91: 1362-1372 [Abstract] [Full Text]
Sobel, E. S., Kakkanaiah, V. N., Schiffenbauer, J., Reap, E. A., Cohen, P. L., Eisenberg, R. A. (1998). Novel Immunoregulatory B Cell Pathways Revealed by lpr-+ Mixed Chimeras. J. Immunol. 160: 1497-1503 [Abstract] [Full Text]
Wang, J., Lenardo, M. J. (1997). Essential Lymphocyte Function Associated 1 (LFA-1): Intercellular Adhesion Molecule Interactions for T Cell-mediated B Cell Apoptosis by Fas/APO-1/CD95. JEM 186: 1171-1176 [Abstract] [Full Text]
Arpin, C., Banchereau, J., Liu, Y.-J. (1997). Memory B Cells Are Biased Towards Terminal Differentiation: A Strategy That May Prevent Repertoire Freezing. JEM 186: 931-940 [Abstract] [Full Text]
Yoshikawa, H., Sakihama, T., Nakajima, Y., Tasaka, K. (1997). Fcgamma RIII-Mediated Regulation of Hematopoiesis in Murine Bone Marrow Cells by Interleukin-3 and CD95 (Fas/Apo-1). Blood 90: 1911-1919 [Abstract] [Full Text]
Mueller, C. G.F., Rissoan, M.-C., Salinas, B., Ait-Yahia, S., Ravel, O., Bridon, J.-M., Briere, F., Lebecque, S., Liu, Y.-J. (1997). Polymerase Chain Reaction Selects a Novel Disintegrin Proteinase from CD40-Activated Germinal Center Dendritic Cells. JEM 186: 655-663 [Abstract] [Full Text]
Liu, Y.-J. (1997). Sites of B Lymphocyte Selection, Activation, and Tolerance in Spleen. JEM 186: 625-629 [Full Text]
Hirose, S., Yan, K., Abe, M., Jiang, Y., Hamano, Y., Tsurui, H., Shirai, T. (1997). Precursor B cells for autoantibody production in genomically Fas-intact autoimmune disease are not subject to Fas-mediated immune�elimination. Proc. Natl. Acad. Sci. USA 94: 9291-9295 [Abstract] [Full Text]
Caux, C., Massacrier, C., Vanbervliet, B., Dubois, B., Durand, I., Cella, M., Lanzavecchia, A., Banchereau, J. (1997). CD34+ Hematopoietic Progenitors From Human Cord Blood Differentiate Along Two Independent Dendritic Cell Pathways in Response to Granulocyte-Macrophage Colony-Stimulating Factor Plus Tumor Necrosis Factor alpha : II. Functional Analysis. Blood 90: 1458-1470 [Abstract] [Full Text]
Kuhne, M. R., Robbins, M., Hambor, J. E., Mackey, M. F., Kosaka, Y., Nishimura, T., Gigley, J. P., Noelle, R. J., Calderhead, D. M. (1997). Assembly and Regulation of the CD40 Receptor Complex in Human B Cells. JEM 186: 337-342 [Abstract] [Full Text]
Genestier, L., Meffre, G., Garrone, P., Pin, J.-J., Liu, Y.-J., Banchereau, J., Revillard, J.-P. (1997). Antibodies to HLA Class I alpha 1 Domain Trigger Apoptosis of CD40-Activated Human B Lymphocytes. Blood 90: 726-735 [Abstract] [Full Text]
Fayette, J., Dubois, B., Vandenabeele, S., Bridon, J.-M., Vanbervliet, B., Durand, I., Banchereau, J., Caux, C., Briere, F. (1997). Human Dendritic Cells Skew Isotype Switching of CD40-activated Naive B Cells towards IgA1 and IgA2. JEM 185: 1909-1918 [Abstract] [Full Text]
Reap, E. A., Roof, K., Maynor, K., Borrero, M., Booker, J., Cohen, P. L. (1997). Radiation and stress-induced apoptosis: A role for Fas/Fas ligand�interactions. Proc. Natl. Acad. Sci. USA 94: 5750-5755 [Abstract] [Full Text]