Role of c-myc and p27 in Anti-IgM Induced B-Lymphoma Apoptosis

  • D. W. Scott
  • D. Donjerković
  • B. Maddox
  • S. Ezhevsky
  • T. Grdina
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 224)


Crosslinking membrane IgM receptors on a set of murine B cell lymphomas leads to a rapid increase in c-myc, followed by a decrease in its expression to undetectable levels by 8–24 hours. These cells die soon thereafter via apoptosis. IgD receptor crosslinking also leads to an increase in c-myc expression, but it remains above baseline levels for more than 24 hours; these cells continue to proliferate and do not die. We previously reported that antisense oligonucleotides for c-myc prevented growth arrest and cell death in these lymphomas, independent of the presence of mitogenic CpG motifs. Indeed, antisense for c-myc actually led to a stabilization of c-myc message and protein. Growth arrest in these cells is dependent on the increased synthesis of the p27 cyclin kinase inhibitor (Kipl) normally induced after anti-IgM crosslinking. Consistent with its biologic effects, anti-IgD does not cause an increase in p27. Since dexamethasone causes a loss of myc and synergizes with the anti-IgM signal, we suggest that accelerated cell death with this steroid in the presence of anti-IgM is due to a more rapid degradation of this oncogene product. Finally, we propose that c-myc drives the transcription or activation of an inhibitor of the p27 Kip (Kipi). Hence, loss of c-myc in response to anti-IgM signals in these B-cell lymphomas leads to upregulation of p27, growth arrest and apoptosis. It follows that maintenance of c-myc in these B-cell lymphomas should lead to survival and no increase in p27.


Growth Arrest Induce Growth Arrest Lymphoma Model Accelerate Cell Death Retinoblastoma Gene Product 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • D. W. Scott
    • 1
  • D. Donjerković
    • 1
  • B. Maddox
    • 1
  • S. Ezhevsky
    • 1
  • T. Grdina
    • 1
  1. 1.Department of Immunology, Holland Laboratory for the Biomedical SciencesAmerican Red CrossRockvilleUSA

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