Title: A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti-IgM-induced cell death
Abstract: European Journal of ImmunologyVolume 29, Issue 10 p. 3077-3088 ArticleFree Access A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti-IgM-induced cell death Andreas W. Kuss, Andreas W. Kuss Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorMatthias. Knödel, Matthias. Knödel Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorFriederike. Berberich-Siebelt, Friederike. Berberich-Siebelt Department of Molecular Pathology, Pathological Institute, University of Würzburg, Würzburg, GermanySearch for more papers by this authorDirk. Lindemann, Dirk. Lindemann Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorAnneliese. Schimpl, Anneliese. Schimpl Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorIngolf. Berberich, Corresponding Author Ingolf. Berberich [email protected] Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanyInstitut für Virologie und Immunbiologie, Versbacher Str. 7, D-97078 Würzburg, Germany Fax: + 49-931-201-2243Search for more papers by this author Andreas W. Kuss, Andreas W. Kuss Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorMatthias. Knödel, Matthias. Knödel Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorFriederike. Berberich-Siebelt, Friederike. Berberich-Siebelt Department of Molecular Pathology, Pathological Institute, University of Würzburg, Würzburg, GermanySearch for more papers by this authorDirk. Lindemann, Dirk. Lindemann Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorAnneliese. Schimpl, Anneliese. Schimpl Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanySearch for more papers by this authorIngolf. Berberich, Corresponding Author Ingolf. Berberich [email protected] Institute of Virology and Immunology, University of Würzburg, Würzburg, GermanyInstitut für Virologie und Immunbiologie, Versbacher Str. 7, D-97078 Würzburg, Germany Fax: + 49-931-201-2243Search for more papers by this author First published: 08 October 1999 https://doi.org/10.1002/(SICI)1521-4141(199910)29:10<3077::AID-IMMU3077>3.0.CO;2-RCitations: 68AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Engagement of the antigen receptor on murine immature B cells leads to growth arrest followed by apoptosis. Concomitant signaling through CD40 sustains proliferation and rescues the cells from apoptosis. We show here that cross-linking CD40 stimulates the expression of A1, a member of the anti-apoptotic Bcl-2 family, in primary murine B lymphocytes. CD40-dependent stimulation of A1 was confirmed in WEHI 231 cells, an immature murine B cell lymphoma line. We transduced WEHI 231 cells with a bicistronic recombinant retroviral vector coding for A1 and a chimeric selection marker comprising the enhanced yellow fluorescent protein and the zeocin resistance protein. A1-transduced WEHI 231 cells showed a significant higher survival rate after engagement of the antigen receptor. In contrast, constitutive expression of A1 did not abrogate anti-IgM-induced c-myc down-regulation. Consistant with this, A1 did not release anti-IgM-induced cell cycle arrest. Our data indicate that CD40-stimulated A1 expression permits WEHI 231 cells to survive in the presence of anti-IgM antibodies and suggests a protective role for A1 in antigen receptor-mediated apoptosis in B cells. References 1 Osmond, D. G. and Nossal, G. J. V., Differentiation of lymphocytes in mouse bone marrow. II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labeling. Cell. Immunol. 1974. 13: 132–145. 2 MacLennan, I. C., B-cell receptor regulation of peripheral B cells. Curr. Opin. Immunol. 1998. 10: 220–225. 3 Healy, J. I. and Goodnow, C. C., Positive versus negative signaling by lymphocyte antigen receptors. Annu. Rev. Immunol. 1998. 16: 645–670. 4 Rolink, A. G., Andersson, J. and Melchers, F., Characterization of immature B cells by a novel monoclonal antibody, by turnover and by mitogen reactivity. Eur. J. Immunol. 1998. 28: 3738–3748. 5 Sater, R. A., Sandel, P. C. and Monroe, J. G., B cell receptor-induced apoptosis in primary transitional murine B cells: signaling requirements and modulation by T cell help. Int. Immunol. 1998. 10: 1673–1682. 6 van Kooten, C. and Banchereau, J., Functions of CD40 on B cells, dendritic cells and other cells. Curr. Opin. Immunol. 1997. 9: 330–337. 7 Smith, C. A., Farrah, T. and Goodwin, R. G., The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 1994. 76: 959–962. 8 Armitage, R. J., Fanslow, W. C., Strockbine, L., Sato, T. A., Clifford, K. N., Macduff, B. M., Anderson, D. M., Gimpel, S. D., Davis, S. T. and Maliszewski, C. R., Molecular and biological characterization of a murine ligand for CD40. Nature 1992. 357: 80–82. 9 Benhamou, L. E., Cazenave, P. A. and Sarthou, P., Anti-immunoglobulins induce death by apoptosis in WEHI-231 B lymphoma cells. Eur. J. Immunol. 1990. 20: 1405–1407. 10 Hasbold, J. and Klaus, G. G., Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas. Eur. J. Immunol. 1990. 20: 1685–1690. 11 Tsubata, T., Wu, J. and Honjo, T., B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40. Nature 1993. 364: 645–648. 12 Gottschalk, A. R. and Quintans, J., Apoptosis in B lymphocytes: the WEHI-231 perspective. Immunol. Cell Biol. 1995. 73: 8–16. 13 Sonenshein, G. E., RelNF-kappa B transcription factors and the control of apoptosis. Semin. Cancer Biol. 1997. 8: 113–119. 14 Lee, H., Arsura, M., Wu, M., Duyao, M., Buckler, A. J. and Sonenshein, G. E., Role of Rel-related factors in control of c-myc gene transcription in receptor-mediated apoptosis of the murine B cell WEHI 231 line. J. Exp. Med. 1995. 181: 1169–1177. 15 Arsura, M., Wu, M. and Sonenshein, G. E., TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha. Immunity 1996. 5: 31–40. 16 Wu, M., Lee, H., Bellas, R. E., Schauer, S. L., Arsura, M., Katz, D., Fitz Gerald, M. J., Rothstein, T. L., Sherr, D. H. and Sonenshein, G. E., Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells. EMBO J. 1996. 15: 4682–4690. 17 Schauer, S. L., Wang, Z., Sonenshein, G. E. and Rothstein, T. L., Maintenance of nuclear factor-kappa B/Rel and c-myc expression during CD40 ligand rescue of WEHI 231 early B cells from receptor-mediated apoptosis through modulation of I kappe B proteins. J. Immunol. 1996. 157: 81–86. 18 Siebelt, F., Berberich, I., Shu, G., Serfling, E. and Clark, E. A., Role for CD40-mediated activation of c-Rel and maintenance of c-myc RNA levels in mitigating anti-IgM-induced growth arrest. Cell. Immunol. 1997. 181: 13–22. 19 Wu, M., Arsura, M., Bellas, R. E., Fitz Gerald, M. J., Lee, H., Schauer, S. L., Sherr, D. H. and Sonenshein, G. E., Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells. Mol. Cell. Biol. 1996. 16: 5015–5025. 20 Chao, D. T. and Korsmeyer, S. J., BCL-2 family: regulators of cell death. Annu. Rev. Immunol. 1998. 16: 395–419. 21 Choi, M. S., Boise, L. H., Gottschalk, A. R., Quintans, J., Thompson, C. B. and Klaus, G. G., The role of bcl-XL in CD40-mediated rescue from anti-mu-induced apoptosis in WEHI-231 B lymphoma cells. Eur. J. Immunol. 1995. 25: 1352–1357. 22 Fang, W., Rivard, J. J., Ganser, J. A., Le Bien, T. W., Nath, K. A., Mueller, D. L. and Behrens, T. W., Bcl-xL rescues WEHI 231 B lymphocytes from oxidant-mediated death following diverse apoptotic stimuli. J. Immunol. 1995. 155: 66–75. 23 Merino, R., Grillot, D. A., Simonian, P. L., Muthukkumar, S., Fanslow, W. C., Bondada, S. and Nunez, G., Modulation of anti-IgM-induced B cell apoptosis by Bcl-xL and CD40 in WEHI-231 cells. Dissociation from cell cycle arrest and dependence on the avidity of the antibody-IgM receptor interaction. J. Immunol. 1995. 155: 3830–3838. 24 Ishida, T., Kobayashi, N., Tojo, T., Ishida, S., Yamamoto, T. and Inoue, J., CD40 signaling-mediated induction of Bel-XL, Cdk4, and Cdk6. Implication of their cooperation in selective B cell growth. J. Immunol. 1995. 155: 5527–5535. 25 Grillot, D. A., Merino, R., Pena, J. C., Fanslow, W. C., Finkelman, F. D., Thompson, C. B. and Nunez, G., bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. J. Exp. Med. 1996. 183: 381–391. 26 Lin, E. Y., Orlofsky, A., Berger, M. S. and Prystowsky, M. B., Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. J. Immunol. 1993. 151: 1979–1988. 27 Karsan, A., Yee, E. and Harlan, J. M., Endothelial cell death induced by tumor necrosis factor-alpha is inhibited by the Bcl-2 family member, A1. J. Biol. Chem. 1996. 271: 27201–27204. 28 D'Sa Eipper, C., Subramanian, T. and Chinnadurai, G., bfl-1, a bcl-2 homologue, suppresses p53-induced apoptosis and exhibits potent cooperative transforming activity. Cancer Res. 1996. 56: 3879–3882. 29 Lin, E. Y., Orlofsky, A., Wang, H. G., Reed, J. C. and Prystowsky, M. B., A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood 1996. 87: 983–992. 30 Tomayko, M. M. and Cancro, M. P., Long-lived B cells are distinguished by elevated expression of A1. J. Immunol. 1998. 160: 107–111. 31 Wu, M., Yang, W., Bellas, R. E., Schauer, S. L., Fitz Gerald, M. J., Lee, H. and Sonenshein, G. E., c-myc promotes survival of WEHI 231 B lymphoma cells from apoptosis. Curr. Top. Microbiol. Immunol. 1997. 224: 91–101. 32 Austen, M., Cerni, C., Henriksson, M., Hilfenhaus, S., Luscher Firzlaff, J. M., Menkel, A., Seelos, C., Sommer, A. and Luscher, B., Regulation of cell growth by the Myc-Max-Mad network: role of Mad proteins and YY1. Curr. Top. Microbiol. Immunol. 1997. 224: 123–130. 33 Grumont, R. J., Rourke, I. J. and Gerondakis, S., Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis. Genes Dev. 1999. 13400–411. 34 Liu, Y. J., Joshua, D. E., Williams, G. T., Smith, C. A., Gordon, J. and MacLennan, I. C., Mechanism of antigen-driven selection in germinal centres. Nature 1989. 342: 929–931. 35 Turner, C. A., Jr., Mack, D. H. and Davis, M. M., Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell 1994. 77: 297–306. 36 Messika, E. J., Lu, P. S., Sung, Y. J., Yao, T., Chi, J. T., Chien, Y. H. and Davis, M. M., Differential effect of B lymphocyte-induced maturation protein (Blimp-1) expression of cell fate during B cell development. J. Exp. Med. 1998. 188: 515–525. 37 Grumont, R. J. and Gerondakis, S., The subunit composition of NF-kappa B complexes changes during B cell development. Cell Growth Differ. 1994. 5: 1321–1331. 38 Miyamoto, S., Schmitt, M. J. and Verma, I. M., Qualitative changes in the subunit composition of kappa B-binding complexes during murine B-cell differentiation. Proc. Natl. Acad. Sci. USA 1994. 91: 5056–5060. 39 Liou, H. C., Sha, W. C., Scott, M. L. and Baltimore, D., Sequential induction of NF-kappa B/Rel family proteins during B-cell terminal differentiation. Mol. Cell. Biol. 1994. 14: 5349–5359. 40 Berberich, I., Shu, G. L. and Clark, E. A., Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. J. Immunol. 1994. 153: 4357–4366. 41 Hanissian, S. H. and Geha, R. S., Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells. Immunity 1997. 6: 379–387. 42 Sakata, N., Patel, H. R., Terada, N., Aruffo, A., Johnson, G. L. and Gelfand, E. W., Selective activation of c-Jun kinase mitogen-activated protein kinase by CD40 on human B cells. J. Biol. Chem. 1995. 270: 30823–30828. 43 Berberich, I., Shu, G., Siebelt, F., Woodgett, J. R., Kyriakis, J. M. and Clark, E. A., Cross-linking CD40 on B cells preferentially induces stress-activated protein kinases rather than mitogen-activated protein kinases. EMBO J. 1996. 15: 92–101. 44 Sutherland, C. L., Heath, A. W., Pelech, S. L., Young, P. R. and Gold, M. R., Differential activation of the ERK, JNK, and p38 mitogen-activated protein kinases by CD40 and the B cell antigen receptor. J. Immunol. 1996. 157: 3381–3390. 45 Grumont, R. J., Rourke, I. J., O'Reilly, L. A., Strasser, A., Miyake, K., Sha, W. and Gerondakis, S., B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-kappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells. J. Exp. Med. 1998. 187: 663–674. 46 Amati, B., Alevizopoulos, K. and Vlach, J., Myc and the cell cycle. Front. Biosci. 1998. 3: D250–268. 47 Han, H., Nomura, T., Honjo, T. and Tsubata, T., Differential modulation of cyclin-dependent kinase inhibitor p27Kip1 by negative signaling via the antigen receptor of B cells and positive signaling via CD40. Eur. J. Immunol. 1996. 26: 2425–2432. 48 Graves, J. D., Draves, K. E., Craxton, A., Krebs, E. G. and Clark, E. A., A comparison of signaling requirements for apoptosis of human B lymphocytes induced by the B cell receptor and CD95/Fas. J. Immunol. 1998. 161: 168–174. 49 Andjelic, S. and Liou, H. C., Antigen receptor-induced B lymphocyte apoptosis mediated via a protease of the caspase family. Eur. J. Immunol. 1998. 28: 570–581. 50 Chen, L., Kim, T. J. and Pillai, S., Inhibition of caspase activity prevents anti-IgM induced apoptosis but not ceramide generation of WEHI 231 B cells. Mol. Immunol. 1998. 35: 195–205. 51 Lens, S. M., den Drijver, B. F., Potgens, A. J., Tesselaar, K., van Oers, M. H. and van Lier, R. A., Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced apoptosis in human B cells. J. Immunol. 1998. 160: 6083–6092. 52 Thornberry, N. A. and Lazebnik, Y., Caspases: enemies within: Science 1998. 281: 1312–1316. 53 Zamzami, N., Susin, S. A., Marchetti, P., Hirsch, T., Gomez-Monterrey, I., Castedo, M. and Kroemer, G., Mitochondrial control of nuclear apoptosis. J. Exp. Med. 1996. 183: 1533–1544. 54 Gottschalk, A. R., Boise, L. H., Thompson, C. B. and Quintans, J., Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bcl-2. Proc. Natl. Acad. Sci. USA 1994. 91: 7350–7354. 55 Green, D. R. and Reed, J. C., Mitochondria and apoptosis. Science 1998. 281: 1309–1312. 56 Hatakeyama, S., Hamasaki, A., Negishi, I., Loh, D. Y., Sendo, F. and Nakayama, K., Multiple gene duplication and expression of mouse bcl-2-related genes, A1. Int. Immunol. 1998. 10: 631–637. 57 Du Bridge, R. B., Taneg, P., Hsia, H. C., Leong, P. M., Miller, J. H. and Calos, M. P., Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol. Cell. Biol. 1987. 7: 379–387. 58 Chen Bettecken, U., Wecker, A. and Schimpl, A., IgM RNA switch from membrane to secretory form is prevented by adding antireceptor antibody to bacterial lipopolysaccharide-stimulated murine primary B-cell cultures. Proc. Natl. Acad. Sci. USA 1985. 82: 7384–7388. 59 Rolink, A., Melchers, F. and Andersson, J., The SCID but not the RAG-2 gene product is required for S mu-S epsilon heavy chain class switching. Immunity 1996. 5: 319–330. 60 Lindemann, D., Patriquin, E., Feng, S. and Mulligan, R. C., Versatile retrovirus vector systems for regulated gene expression in vitro and in vivo. Mol. Med. 1997. 3: 466–476. 61 Soneoka, Y., Cannon, P. M., Ramsdale, E. E., Griffiths, J. C., Romano, G., Kingsman, S. M. and Kingsman, A. J., A transient three-plasmid expression system for the production of high liter retroviral vectors. Nucleic Acids Res. 1995. 23: 628–633. Citing Literature Volume29, Issue10October 1999Pages 3077-3088 ReferencesRelatedInformation