In studies concerning the interaction of B-CLL cells and Epstein-Barr virus (EBV), we encountered one patient whose cells had several unusual properties. In addition to the B-cell markers, the CLL cells expressed the exclusive T-cell markers CD3 and CD8 and carried a translocation t(18,22)(q21; q11), involving the bcl-2 and Igl loci. The patient represents the 4th reported CLL case with this translocation. The CLL cells could be infected and immortalized by the indigenous and by the prototype B958 virus in vitro. The T-cell markers were not detectable on the established lines. In all experiments the immortalized lines originated from the CLL cells. Their preferential emergence over virus-infected normal B cells may be coupled to the high expression of the bcl-2 gene due to the translocation. In spite of the sensitivity of CLL cells to EBV infection in vitro, no EBNA-positive cells were detected in the ex vivo population. In vitro, we could generate cytotoxic function in T-lymphocyte cultures which acted on autologous EBV-infected CLL cells. Therefore we assume that if such cells emerged in vivo they were eliminated by the B-CLL is a disease characterized by the accumulation of B lymphocytes in variable maturation stages. The leukemic population is of clonal origin. The majority of B-CLL clones (patients) express CD5, a common T-cell marker. This surface molecule is also carried by a minor B-cell sub-set in the mantle zone of secondary follicles (Caligaris-Cappio et al., 1993). Therefore it has been proposed that the B-CLLs originate from this B-cell sub-set (Nilsson, 1992).B-CLL is the most common form of leukemia in adults. Some studies have attempted to correlate the finer phenotypic characteristics of the cells, such as expression of B-and T-cell markers, HLA and integrin molecules, complement and Fc receptors, also production of various cytokines, with the clinical course of the disease.The current hypothesis is that faulty regulation of bcl-2 gene expression plays a major role in the accumulation of the CLL cells, and thus the physiological dynamics of proliferation and survival of B cells is disturbed. Compared with normal B cells, bcl-2 expression is high in the CLL cells. The underlying molecular mechanisms are not known; hypomethylation of the gene has been proposed as being responsible for cases in which chromosomal translocations could not explain the high bcl-2 protein level (Hanada et al., 1993).In addition to the analysis of ex vivo CLL cells, their behavior and response to various stimuli in vitro also provided differentiating features. The initial observation showing that CLL cells can be induced to leave the resting stage was the most important step in these studies. At least 50% of the clones are inducible to proliferation and/or differentiation by TPA and physiological inducers, e.g., SAC, anti-IgM, IL-2, IL-4 and TNF-a (Nilsson, 1992).EBV is not involved in the etiology of B-CLL. The cells are practically resistant to the immortalizing capacity of EBV, though they can be infected in vitro. No...
