Mammalian chimaeras / Anne McLaren.

  • McLaren, Anne.
Date:
[1976]
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Mammalian chimaeras / Anne McLaren. Source: Wellcome Collection.

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    78 Immunology and blood marrow, thymus and Payer's patches, far from being homogeneous, were all different, as were spleen and lymph nodes. Presumably the selective advantage of the AKR genotype varied from tissue to tissue and determined the balance between the two cell populations, outweighing any initial resemblances due to stem-cell origins, and any differences due to founder effects. The AKR strain is known to be highly susceptible to spontaneous thymus-associated lym¬ phoma (see Chapter 8). A further complication is introduced by the observations of Bona et al. (1974) on the same series of AKRwCBA chimaeras. When the two lympho¬ cyte populations were distinguished not by their chromosomes but by their theta antigens, using immunoautoradiography, the proportions were much more equal, ranging from 24 % to 76 % AKR, with a mean of 46 %. In contrast to control animals, no cells in the chimaeras carried both antigens, implying that cell hybridization seldom if ever occurs. The contradiction between the theta antigen and the chromosomal results could be reconciled if the high proliferative rate of AKR cells in response to PHA in vitro were associated with a relatively low rate of spontaneous proliferation in vivo, or if a high rate of spontaneous proliferation were balanced by a high rate of cell death. In either case, the antigenic analysis would provide a more accurate picture of the actual balance of cellular forces in the tissue than the chromo¬ somal studies. The possibility remains, however, that the theta phenotype of a cell does not always reflect its genotype. The conclusion that little or no cell hybridization occurs within the lym- phomyeloid complex is further supported by observations on two rabbit chimaeras (Gardner & Munro, 1974). When allotype markers on the immunoglobulin heavy and light chains were examined, no mixed mole¬ cules were found, with a limit of detection of 1/300 (A. J. Munro & R. L. Gardner, personal communication). A similar study on allotypes in chimaeric mice from strains differing at the H-2 locus suggests that somatic cell hybridization does sometimes occur (Munro, Day & Gardner, 1974), but the result requires confirmation and other explanations of the data are possible. Tolerance We have seen that the two component cell populations of a chimaera retain their antigenic specificity, and that the chimaerism extends to the immune system. Since the animals are healthy and long-lived, it follows that each component must be in some way immunologically 'tolerant' of the other. The mechanism of this tolerance is still not known. In chimaeras made from inbred embryos the tolerance is specific, in that it extends to tissues from other individuals of the component strains, but not to unrelated strains. Thus chimaeras of several strain combinations were shown to accept skin grafts from the two component strains, but rejected