Mammalian chimaeras / Anne McLaren.

  • Anne McLaren
Date:
[1976]
Catalogue details
    141/168 page 131
    Perspectives 131 Thus, if a C3H<->C57BL chimaera showed around 80 % of allotype H-2'' (C57BL) in both T and В cells reacting with one particular antigen, with other percentages for other antigens, it would suggest that antigenic specificities had become established in lymphoid ontogeny before the divergence of T and В cell lines. Conversely, if all T cell populations resembled one another more closely than they did the antigenically corresponding В cell types, one could conclude that the allocation of T and В cells had occurred before the appearance of antigenic specificity. The phenomenon of allelic exclusion in antibody-forming cells may give rise to mosaicism in heterozygous animals. A comparison of such mosaics with appropriate chimaeras might yield information on the relationship between allelic exclusion and the establishment of immunological specificity. As mentioned in Chapter 7, there is at present no unanimity as to the basis for mutual unresponsiveness between the component lymphomyeloid popula¬ tions in chimaeras. The concept of primary tolerance has been challenged, but the demonstration of blocking antibody has yet to be experimentally confirmed. The present conflict of evidence is particularly unsatisfactory, since the mechanisms underlying such a fundamental phenomenon as self- recognition seem unlikely to be strain-specific or even species-specific. If, as has been suggested, some strain combinations are genetically incompetent at developing or maintaining mutual tolerance, analysis of the causes of this defect could throw light on the aetiology of autoimmune diseases in Man. When we turn to phenotypic interactions between genetically distinct cell populations, the value of chimaeras becomes still more obvious. Measure¬ ments of patch size, as have been made on the pigmented retina for example, can now be converted to estimates of clone size; these provide a sensitive indicator of the tendency of cells to stick together. One chimaeric strain com¬ bination has so far been identified in which cells of like genotype tend per- ferentially to stick together. This is particularly striking, since tests of cell aggregation in vitro have in the main shown difi'erential aggregation with respect to tissue origin (e.g. neural retina, heart, kidney) rather than geno¬ type. Presumably difi'erential aggregation reflects differences in cell surface conformation; since surface similarities may be required for normal cell interaction, one wonders whether chimaeras of some genetically divergent strain combinations may turn out to be not entirely representative of normal embryonic development. For experimental embryology studies, using genetic differences between chimaera components as markers to facilitate the analysis of cell lineage, the residual genetic differences between components should be as small as possible so as to ensure that development is as normal as possible. Congenie strains, diff'ering only at a single locus, provide ideal material. When we are con¬ sidering the role of genetic diff'erences in cell-to-cell interaction, on the other hand, genetic divergence between the components may prove more informa-
    No text description is available for this image
    No text description is available for this image
    No text description is available for this image