Subtelomeric as well as telomeric sequences are lost from chromosomes in proliferating B lymphocytes

B lymphocytes purified from peripheral blood can be normally cultured in vitro for only one doubling. They can undergo an unlimited number of cell divisions after transformation with a DNA tumor virus such as the Epstein-Barr virus. We have shown that the terminal restriction fragments of virus transformed B lymphocytes are shortened in the course of proliferation and that this process is accompanied by structural modifications. We have identified the sequences that are lost during the shortening process by hybridization to the canonical human telomeric simple repeat TTAGGG, to other simple sequences that are found at the ends of human chromosomes, and to a human subtelomeric sequence. We have observed that by 20 doublings over half the TTAGGG sequences, but few or no TGAGGG sequences, are lost from the TRFs. The subtelomeric sequence was removed from most of the TRFs on which it was present. The implications that these observations have on the problems of cell senescence and oncology are discussed.