In vitro studies on human lymphoid cells in relation to malignant, genetic and immunological disease

• Main Author: Steel, C. Michael
• Published: University of Edinburgh 1988
• Subjects: 611
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662388

The collection of published papers presented for the degree of Doctor of Science covers some eighteen years of work chiefly with human lymphoid cells in long and short-term culture. Many of the papers deal directly with aspects of malignancy, particularly the lymphomas. The distinction between immortalisation and malignant change is explored in terms of cell phenotype and in relation to cytogenetics and molecular genetics. The development and application of a mouse xenotransplantation assay for tumorigenicity (in lymphoid and other cell types) is described. The use of permanent lymphoid cell lines as a renewable source of material representing the genetic consitution of individual patients is illustrated in a number of the papers. The genetic stability of such transformed lines is assessed and contrasted with the relative genetic instability of lymphoma or leukaemia-derived lines. Both types of line are shown to be of value in studies of human genetic disease, the more stable variety providing material for genetic linkage analyses and for detailed examination of the molecular basis of any genetic disorder from which the cell line donor may have suffered. Genetic instability <i>in vitro</i>, on the other hand, can be exploited to analyse spontaneous or induced mutations which throw light on gene localisation and on the relationship between gene structure and function. The classification of lymphoid cells into functionally and phenotypically distinct subgroups has advanced enormously in the period covered by these papers, several of which contribute to that process. There are, for example, original studies on age-related changes in the proportions of different lymphocyte subsets in the circulation and on short-term changes with physical exercise. Abnormalities of circulating lymphocyte subsets are demonstrated in diseases affecting the immune system, notably in infectious mononucleosis and, more recently, in AIDS. The whole collection of papers, while covering a wide field, has as its unifying theme the author's primary interest, namely the initiation and evolution of lymphoid malignancy in man.