In this study we have raised the question of whether DNA can be transferred
from one cell to another by phagocytosis of apoptotic bodies. We have used
integrated copies of the Epstein-Barr virus (EBV) as a marker to follow th
e fate and expression pattern of apoptotic DNA in the phagocytotic host. Ap
optosis was induced in EBV-carrying cell lines by irradiation before cultiv
ation with either human fibroblasts, macrophages, or bovine aortic endothel
ial cells. Analysis of the expression pattern of EBV-encoded genes was perf
ormed by immunofluorescent staining as well as in situ hybridization. Cocul
tivation of apoptotic bodies from lymphoid cell lines containing integrated
but not episomal copies of EBV resulted in expression of the EBV-encoded g
enes EBER and EBNA1 in the recipient cells at a high frequency. Fluorescenc
e in situ hybridization analysis showed uptake of human chromatin as well a
s integrated EBV-DNA into the nuclei of bovine aortic endothelial cells, Th
ese data show that DNA may be rescued and reused from apoptotic bodies by s
omatic cells. In addition, our findings suggest that apoptotic bodies deriv
ed from EBV-carrying B lymphocytes may serve as the source of viral transfe
r to cells that lack receptors for the EBV virus in vivo, (C) 1999 by The A
merican Society of Hematology.