DECREASED PROTEIN-LEVELS OF THE C-CBL PROTOONCOGENE IN MURINE AIDS

Murine acquired immunodeficiency syndrome (MAIDS) can be viewed as a l ymphoproliferative disease which involves B cells as well as T cells f rom spleen and lymph nodes while thymus and Peyer's patches do not par ticipate in the process. The 120-kDa protooncogene product c-Cbl was i nitially cloned from the murine Cas NS-1 B cell lymphoma, It is a main target of immunoreceptor (TCR and BCR)-mediated protein tyrosine kina se activity. Moreover, recent data suggest that c-Cbl might play a cru cial role in the regulation of cell proliferation through regulation o f GTP-binding proteins. Therefore, the involvement of c-Cbl was evalua ted in the lymphoproliferative disease induced by the MAIDS virus. The expression of the c-Cbl protein was dramatically reduced in the lymph node of infected mice while it remained normal in the thymus. In cont rast, the expression of actin, TCR-zeta chain, ZAP-70, and p59(fyn) re mained similar in controls and infected mice. Identical results were o btained with sorted B cells and T cells. Surprisingly, a B cell lympho ma line derived from late stage MAIDS mice displayed a normal level of c-Cbl. (C) 1998 Academic Press.