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Increased p27^Kip1 Cyclin-Dependent Kinase Inhibitor Gene Expression Following Anti-IgM Treatment Promotes Apoptosis of WEHI 231 B Cells¹

Min Wu^2,*, Robert E. Bellas^2,*, Jian Shen^2,, William Yang^* and Gail E. Sonenshein^3,*

Departments of ^* Biochemistry and Laboratory Medicine and Pathology, Boston University Medical School, Boston MA 02118

Engagement of the B cell receptor of WEHI 231 immature B cells leads sequentially to a drop in c-Myc, to induction of the cyclin-dependent kinase inhibitor p27^Kip1, and finally to apoptosis. Recently we demonstrated that the drop in c-Myc expression promotes cell death, whereas the induction of p27 has been shown to lead to growth arrest. In this paper, we demonstrate that increased p27 expression also promotes apoptosis of WEHI 231 B cells. The rescue of WEHI 231 cells by CD40 ligand engagement of its receptor prevented the increase in p27 induction. Inhibition of p27-ablated apoptosis induced upon expression of antisense c-myc RNA. Furthermore, specific induction of p27 gene expression resulted in apoptosis of WEHI 231 cells. Lastly, inhibition of expression of c-Myc, upon induction of an antisense c-myc RNA vector, was sufficient to induce increased p27 levels and apoptosis. Thus, these findings define a signaling pathway during B cell receptor engagement in which the drop in c-Myc levels leads to an increase in p27 levels that promotes apoptosis.

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