Epstein-Barr virus transforms precursor B cells even before immunoglobulin gene rearrangements

The very early stages of the human B-cell differentiation pathway are poorly understood, primarily because of the lack of appropriate permanent cell lines. Epstein–Barr virus (EBV) is a putative human oncogenic virus which transforms human B cells in vitro into continuously proliferating cells 1 . It has been believed that EBV transforms mature B cells 2,3 but recently, transformation of immature pre-B-cell lines has been reported 4–6 , suggesting that EBV might also transform cells much earlier in the B-cell lineage. We report here the establishment of cell lines transformed by EBV at various stages of the B-cell differentiation pathway. Interestingly, two lines showed the complete absence of immunoglobulin synthesis and the lack of immunoglobulin gene rearrangement despite containing EBV genome and surface markers of B cells. Our results indicate that EBV can infect and tranform cells of the B lymphocyte lineage even before immunoglobulin gene rearrangement.