Signaling through the antigen receptor of B lymphocytes activates a p53-independent pathway of c-Myc-induced apoptosis

Deregulated expression of c-Myc has been shown to induce or enhance apoptos is in various different cell types, c-Myc requires p53 for apoptosis in som e but not all the cell types, indicating heterogeneous mechanisms for c-Myc -induced apoptosis, In B lymphoma line WEHI-231, stable expression of c-Myc has been demonstrated to protect cells from BCR-mediated apoptosis. Howeve r, stable expression of c-Myc carrying pro-apoptotic functions may generate variant cells resistant to apoptosis. By utilizing an inducible system for c-Myc, me demonstrated here that deregulated expression of c-Myc induced a poptosis of WEHI-231 by itself, indicating that c-Myc induces apoptosis in WEHI-231 as is the case for other cell types. When transactivation of p53 w as inactivated, WEHI-231 cells overexpressing c-Myc no longer underwent apo ptosis in the absence of other stimuli, but showed markedly enhanced apopto sis in the presence of BCR ligation. These results indicate that deregulate d c-Myc expression enhances apoptosis by a p53-independent pathway in the p resence of BCR signaling but requires p53 for apoptosis in the absece of BC R crosslinking in WEHI-231, BCR ligation may thus activate a p53-independen t pathway of Myc-induced apoptosis.