This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McDonnell, T J
Right arrow Articles by Korsmeyer, S J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McDonnell, T J
Right arrow Articles by Korsmeyer, S J

 Previous Article  |  Next Article 

Mol Cell Biol. 1990 May; 10(5): 1901-1907

Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population.

T J McDonnell, G Nunez, F M Platt, D Hockenberry, L London, J P McKearn and S J Korsmeyer

Howard Hughes Medical Institute, St. Louis, Missouri.

ABSTRACT

We characterized the basis for the follicular lymphoproliferation in transgenic mice bearing a Bcl-2-immunoglobulin (Bcl-2-Ig) minigene representing the t(14;18) of human follicular lymphoma. Discriminatory S1 nuclease protection assays revealed that the Bcl-2-Ig transgene was overexpressed relative to endogenous mouse Bcl-2 in spleen and thymus. Western (immunoblot) analysis demonstrated the overproduction of the human 25-kilodalton Bcl-2 protein, which arose from the transgene, in spleen, thymus, and the expanded B-cell subset. Despite the generalized lymphoid pattern of deregulation, two-color flow cytometry and density gradient centrifugation indicated that the expanded lymphocytes were predominantly small, resting B cells coexpressing B220, immunoglobulin M (IgM), IgD, Ia, and kappa. Cell cycle analysis confirmed that about 97% of these expanded B cells reside in G0/G1. An extensive characterization of transgenic lines revealed a fourfold excess of IgM-IgD-expressing B cells in spleen and dramatically increased numbers in bone marrow. While resting, these cells proliferated in response to lipopolysaccharide and anti-IgM and demonstrated normal B-cell colony formation in soft agar. Moreover, these B cells, which demonstrated an extended survival in vitro even in the absence of stroma, were also resting in G0, yet were capable of proliferative responses. These findings provide consistent evidence that the accumulation of B cells after Bcl-2 overproduction is secondary to prolonged cell survival and not increased cell cycling. This suggests a unique role for Bcl-2 as a proto-oncogene that enhances cell survival independent of promoting cell division.

Mol Cell Biol. 1990 May; 10(5): 1901-1907




This article has been cited by other articles:

  • Chattopadhyay, G., Khan, A. Q., Sen, G., Colino, J., duBois, W., Rubtsov, A., Torres, R. M., Potter, M., Snapper, C. M. (2007). Transgenic Expression of Bcl-xL or Bcl-2 by Murine B Cells Enhances the In Vivo Antipolysaccharide, but Not Antiprotein, Response to Intact Streptococcus pneumoniae. J. Immunol. 179: 7523-7534 [Abstract] [Full Text]  
  • Iqbal, J., Neppalli, V. T., Wright, G., Dave, B. J., Horsman, D. E., Rosenwald, A., Lynch, J., Hans, C. P., Weisenburger, D. D., Greiner, T. C., Gascoyne, R. D., Campo, E., Ott, G., Muller-Hermelink, H. K., Delabie, J., Jaffe, E. S., Grogan, T. M., Connors, J. M., Vose, J. M., Armitage, J. O., Staudt, L. M., Chan, W. C. (2006). BCL2 Expression Is a Prognostic Marker for the Activated B-Cell-Like Type of Diffuse Large B-Cell Lymphoma. JCO 24: 961-968 [Abstract] [Full Text]  
  • Yeh, T.-Y., Chuang, J.-Z., Sung, C.-H. (2005). Dynein light chain rp3 acts as a nuclear matrix-associated transcriptional modulator in a dynein-independent pathway. J. Cell Sci. 118: 3431-3443 [Abstract] [Full Text]  
  • Langenau, D. M., Jette, C., Berghmans, S., Palomero, T., Kanki, J. P., Kutok, J. L., Look, A. T. (2005). Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish. Blood 105: 3278-3285 [Abstract] [Full Text]  
  • Donahue, A. C., Hess, K. L., Ng, K. L., Fruman, D. A. (2004). Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85{alpha}. Int Immunol 16: 1789-1798 [Abstract] [Full Text]  
  • Rahman, Z. S. M., Manser, T. (2004). B Cells Expressing Bcl-2 and a Signaling-Impaired BAFF-Specific Receptor Fail to Mature and Are Deficient in the Formation of Lymphoid Follicles and Germinal Centers. J. Immunol. 173: 6179-6188 [Abstract] [Full Text]  
  • Sanchez-Beato, M., Sanchez-Aguilera, A., Piris, M. A. (2003). Cell cycle deregulation in B-cell lymphomas. Blood 101: 1220-1235 [Abstract] [Full Text]  
  • Cancro, M. P., Sah, A. P., Levy, S. L., Allman, D. M., Schmidt, M. R., Woodland, R. T. (2001). xid mice reveal the interplay of homeostasis and Bruton's tyrosine kinase-mediated selection at multiple stages of B cell development. Int Immunol 13: 1501-1514 [Abstract] [Full Text]  
  • Zhou, P., Levy, N. B., Xie, H., Qian, L., Lee, C.-Y. G., Gascoyne, R. D., Craig, R. W. (2001). MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes. Blood 97: 3902-3909 [Abstract] [Full Text]  
  • Willis, T. G., Dyer, M. J. S. (2000). The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies. Blood 96: 808-822 [Full Text]  
  • Waters, J. S., Webb, A., Cunningham, D., Clarke, P. A., Raynaud, F., di Stefano, F., Cotter, F. E. (2000). Phase I Clinical and Pharmacokinetic Study of Bcl-2 Antisense Oligonucleotide Therapy in Patients With Non-Hodgkin's Lymphoma. JCO 18: 1812-1823 [Abstract] [Full Text]  
  • Hsu, S. Y., Hsueh, A. J. W. (2000). Tissue-Specific Bcl-2 Protein Partners in Apoptosis: An Ovarian Paradigm. Physiol. Rev. 80: 593-614 [Abstract] [Full Text]  
  • Jacobs, J. J.L., Scheijen, B., Voncken, J.-W., Kieboom, K., Berns, A., van Lohuizen, M. (1999). Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev. 13: 2678-2690 [Abstract] [Full Text]  
  • Doostzadeh-Cizeron, J., Evans, R., Yin, S., Goodrich, D. W. (1999). Apoptosis Induced by the Nuclear Death Domain Protein p84N5 Is Inhibited by Association with Rb Protein. Mol. Biol. Cell 10: 3251-3261 [Abstract] [Full Text]  
  • Macpherson, N., Lesack, D., Klasa, R., Horsman, D., Connors, J. M., Barnett, M., Gascoyne, R. D. (1999). Small Noncleaved, Non-Burkitt's (Burkitt-Like) Lymphoma: Cytogenetics Predict Outcome and Reflect Clinical Presentation. JCO 17: 1558-1558 [Abstract] [Full Text]  
  • Lapointe, J., Fournier, A., Richard, V., Labrie, C. (1999). Androgens Down-Regulate bcl-2 Protooncogene Expression in ZR-75-1 Human Breast Cancer Cells. Endocrinology 140: 416-421 [Abstract] [Full Text]  
  • Zhou, P., Qian, L., Bieszczad, C. K., Noelle, R., Binder, M., Levy, N. B., Craig, R. W. (1998). Mcl-1 in Transgenic Mice Promotes Survival in a Spectrum of Hematopoietic Cell Types and Immortalization in the Myeloid Lineage. Blood 92: 3226-3239 [Abstract] [Full Text]  
  • Middleton, G., G. P. Pinon, L., Wyatt, S., Davies, A. M. (1998). Bcl-2 Accelerates the Maturation of Early Sensory Neurons. J. Neurosci. 18: 3344-3350 [Abstract] [Full Text]  
  • Wang, D.-G., Johnston, C. F., Marley, J. J., Phenix, K. V., Atkinson, A. B., Russell, C. F. J., Buchanan, K. D. (1997). Expression of the Apoptosis-Suppressing Gene BCL-2 in Pheochromocytoma is Associated with the Expression of C-MYC. J. Clin. Endocrinol. Metab. 82: 1949-1952 [Abstract] [Full Text]  
  • Pinon, L., Middleton, G, Davies, A. (1997). Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development. Development 124: 4173-4178 [Abstract]  
  • Furuchi, T, Masuko, K, Nishimune, Y, Obinata, M, Matsui, Y (1996). Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia. Development 122: 1703-1709 [Abstract]  
  • Chen, Y Y, Wang, L C, Huang, M S, Rosenberg, N (1994). An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement.. Genes Dev. 8: 688-697 [Abstract]  
  • Merry, D., Veis, D., Hickey, W., Korsmeyer, S. (1994). bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS. Development 120: 301-311 [Abstract]  
  • Yin, X.-M., Oltvai, Z.N., Veis-Novack, D.J., Linette, G.P., Korsmeyer, S.J. (1994). Bcl-2 Gene Family and the Regulation of Programmed Cell Death. Cold Spring Harb Symp Quant Biol 59: 387-393 [Abstract]  
  • Adams, J., Cory, S (1991). Transgenic models of tumor development. Science 254: 1161-1167 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»