Regulation of growth of B lymphoma by CD40, CD54lCAM-1, CD95 and CD95L

Abstract

The effect of CD40, CD54/ICAM-1 and CD95 (Fas/APO-1) ligation in murine B lymphomas was investigated. Crosslinking ligation of CD40 induced p53, the p53-regulated CDKI p21Cip1/Waf1, and apoptosis in 3 lymphoma cell lines of a mature phenotype (A20, M12 and TA3), but not in 2 lymphomas of an immature phenotype (WEHI-279 and WEHI-231). Association of Mdm2 with p53 was reduced in A20. Expression of Bax and Bcl-2 was unaffected by CD40 ligation in all lines. Ligation of CD95 induced apoptosis in A20, not in M12, TA3 or WEHI-279. Crosslinking ICAM-1 on A20 had no effect on growth, but induced tyrosine phosphorylation of a 90--100KDa band in ICAM-1 immunoprecipitates, consistent with ICAM-1 itself. My results demonstrate that CD40 and CD95 differentially affect B cell lymphomas according to their developmental stage and show the potential for tumor suppression by signals that promote growth of non-transformed B cells