P. K. Vogt

Prominent progress in molecular biology was only made when it became possible to separate functionally distinct molecules by taking advantage of their biophysical properties. Likewise, the analysis of the functions of hetero­ geneous populations of immunocompetent cells, as to the functional properties of their various subpopulations, can not be done until these can be isolated in reasonably pure form by selective fractionation. During the last few years significant advances have been made in this field, and cells have been separated according to size, density or charge (MILLER et aI. , 1969; SHORTMAN, 1968; ANDERSSON, 1973 c), or by taking advantage of more specific surface markers to allow selective depletion or enrichment of a given subpopulation of cells (WIGZELL and ANDERSSON, 1971). Although separation techniques have been used in a variety of cellular systems, they have been particularly useful in the study of reticuloendothelial cells and primarily in the study of cells partici­ pating in the immune responses. Quite extensive reviews have been written which well cover the methods used for separation of cells and the results obtained with the various approaches (WIGZELL and ANDERSSON, 1971; SHORTMAN, 1972). To review this work is becoming a more and more voluminous task. As data rapidly accumulate, we will not try to make such a complete review.

The study of the genetic regulation of immune response to natural multidetermi­ nant immunogens was undertaken by the method of bidirectional selective breed­ ing of High or Low antibody responder lines of mice. Five Selections are described: Selection I, carried out for agglutinin responsiveness to sheep erythrocytes and pigeon erythrocytes alternated in each generation. Selection II, carried out for agglutinin responsiveness to sheep erythrocytes repeated in each generation. Selection III and Selection IV performed respectively for agglutinin response to flagellar or somatic antigens of Salmonella typhimurium and Salmonella oranienburg alternated in each generation. Selection V, performed for passive agglutinin response to bovine serum albumin and rabbit gamma globulin alternated in each generation. In each Selection the character investigated is polygenic. High and Low responder lines diverge progressively during the selective breeding. The maximal interline separation (selection limit) is reached in the 7th-16th generations. High and Low responder lines at selection limit are considered homozygous for the character submitted to se~ection. Their variance is therefore only due to environ­ mental effects. The difference in agglutinin titre between High and Low lines is 220-fold in Selection I, 103-fold in Selection II, 90-fold in Selection III, 85-fold in Selection IV and 275-fold in Selection V. The partition of genetic and environmental variances in the foundation popu­ lations of the five Selections is established. The proportion of genetic variance is 60% in Selection I; 49% in Selection II; 51% in Selection III; 47% in Selection IV and 76% in Selection V.

The processes involved in herpesvirus replication, latency, and oncogenic transformation, have, in general, been rather poorly defined. A primary reason for this is the size and complexity of the herpesvirus genome. Undoubtedly, a better understanding of the functions of the viral genome in infected and transformed cells will be achieved through studies with temperature-sensitive (ts) mutants of herpesviruses since, theoretically, any essential gene function can be affected by mutants of this type. A. The Herpesviruses A consideration of the genetic analysis of members of the herpesvirus group necessitates a description, albeit brief, of the properties of the group and, most importantly, of their genetic material. The herpesviruses comprise a group of relatively large (100-150 nm), enveloped viruses. The envelope surrounds an icosahedral capsid enclosing a core which contains double­ stranded DNA (ROIZMAN, 1969). The group is thus defined on the basis of a common virion morphology. In addition to a common structure, members of the group share a number of biological properties such as a similar replicative cycle, the ability to cause latent and chronic infections, and the ability to induce antigenic modifications of infected cell membranes. Several herpes­ viruses have been associated recently with malignancies in man and animals (KLEIN, 1972). Herpesviruses are ubiquitous and have been described in over 30 different species (HUNT and MELENDEZ, 1969; WILDY, 1971; FARLEY et aI. , 1972; KAZAMA and SCHORNSTEIN, 1972; NAHMIAS et aI. , 1972; ROlZMAN et aI. , 1973). Their widespread occurrence in nature suggests a common ancestor.