Increased p27(Kip1) cyclin-dependent kinase inhibitor gene expression following anti-IgM treatment promotes apoptosis of WEHI 231 B cells

Engagement of the B cell receptor of WEHI 231 immature B cells leads sequen tially to a drop in c-Myc, to induction of the cyclin-dependent kinase inhi bitor p27(Kipl), and finally to apoptosis. Recently we demonstrated that th e drop in c-Myc expression promotes cell death, whereas the induction of p2 7 has been shown to lead to growth arrest. In this paper, we demonstrate th at increased p27 expression also promotes apoptosis of WEHI 231 B cells. Th e rescue of WEHI 231 cells by CD40 ligand engagement of its receptor preven ted the increase in p27 induction. Inhibition of p27-ablated apoptosis indu ced upon expression of antisense c-myc RNA. Furthermore, specific induction of p27 gene expression resulted in apoptosis of WEHI 231 cells. Lastly, in hibition of expression of c-Myc, upon induction of an antisense c-myc RNA v ector, was sufficient to induce increased p27 levels and apoptosis, Thus, t hese 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 p romotes apoptosis.