Restricted expression of EBV encoded proteins in in vitro infected CLL cells.

CLL is not associated with EBV. CLL cells separated from blood express CR2, the complement receptor that serves also as EBV receptor. Thus CLL cells can be infected in vitro with the virus, however, in contrast to normal B lymphocytes, only rare CLL clones yield transformed lines. This is due to a restricted EBV encoded protein expression in the CLL cells, they express EBNAs, the virus encoded proteins that are localized in the nucleus, but not the cell membrane associated LMP-1, that is also pivotal for the virus induced transformation of B lymphocytes. This expression pattern seems to be unique to a defined B cell maturation window that is represented by the CLL cells. We named this restricted viral expression as Type IIb. Such B lymphocytes have been encountered in lymphoid tissues of infectious mononucleosis (IM) and in post transplant lymphoproliferative disease (PTLD). Moreover, they were shown in tissues of EBV infected "humanized" mice. The EBV encoded protein expression pattern may serve as a marker for the B cell differentiation stage from which CLL clones can develop.