Study of human lymphoblastoid cell lines in tissue culture
Steel, Christopher Michael
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The properties and potential applications of human lymphoblastoid cell linen have been investigated. Buch lines have been established by others from Burkitt's lymphoma tissue, from leukaetnic patients, from those with infectious mononucleosis and latterly from healthy subjects. There is an association between EB virus (Herpes-like virus of Epstein and Barr) and the growth of human lymphob1astold cell lines in vitro. The same virus is linked sero-epidemiologically with Burkitt's lymphoma, nasopharyngeal carcinoma, infectious mononucleosis and a number of other diseases of man. The exact role of the virus both in vivo and in vitro is a matter of some controversy. Using a simple culture technique, 40 cell lines were established from the peripheral blood leukocytes of a diaqnostically rai3:»d group of patients, from normal cord blood and from one h althy adult. 25 of these cultures were initiated by adding EB virus (in the form of lethally irradiated cells of a virus-positive line) to the fresh blood leukocytes. Evidence from experiments of this type suggest that EB virus has a lyraphoproliferative action in vitro. The cell lines are morphologically etlmost indistinguishable. They resemble primitive cells of the lymphoid series and appear to have the property of indefinite growth in vitro. They include some phagocytic cells and immunoglobulins are released into the culture medium. Feu of the lines were chromosomally abnormal when examined shortly after establishment but all of those examined after more than 1 year of continuous growth had abnormal karyotypes. There was no evidence for the recurrence of any specific chromosome aberration in a significant proportion of the lines. Antigenleally the established lines differ from the original donor's fresh lymphocytes. This is shown by measurement of tritiated thymidine uptake by lymphocytes exposed in vitro to irradiated cells from an autochthonous line. Together with the activation process, the fresh lymphocytes acquire cytotoxic potential directed specifically against the cell line used in the activation phase. Tt is suggested that this system constitutes a model for an immunological surveillance mechanism operating in vivo to eliminate deviant cells. Cell lines of this type offer rcone for detailed investiga¬ tion of the induction of proliferation in human tissue (in this case probably by FB virus) and of the immunological processes by which altered autochthonous cells may be recognised and destroyed. Both of these topics are relevant to the basic study of malignant disease. The prolonged life span and relative stability of these lines in vitro also presents opportunities in the Field of human genetics, both for the investigation of inherited disorders of man and, experimentally, for the measurement of spontaneous and induced mutation rates, analysis of gene linkage and chromosome mapping.