Info

2—4

TR, total response to selection; h2, realized heritability; n, number of independent loci.

TR, total response to selection; h2, realized heritability; n, number of independent loci.

similarity in the total response to selection, selection limit and realized heritability. Only in selection V was the total response greater and attained after fewer generations. The number of independent loci controlling antibody responsiveness differed in the five selections, owing to the different nature of the antigens and immunization procedures used. Mapping studies associating polymorphic microsatellite markers with antibody response in selection I have shown that some segregating loci are linked to genes on chromosomes 4 and 8 but also to genes certainly involved in major immune functions, such as genes on chromosome 6 coding for the TCR (3 chain, Igx and CD8, genes on chromosome 12 coding for the Igh allotypes, and genes on chromosome 17 coding for the MHC, TNFa, TNF0, C2 and C.4.

The antibody response in H, L lines, and interline hybrids of the five selections (Table 2), indicates that the additive effect (a) was similar, whereas the dominance deviation (d) was different in all selections, yielding a different dominance effect (d/a) in each selection. Thus, the high responsiveness was incompletely dominant, to a variable extent, in selections I, II, III and IV, whereas it was incompletely recessive in selection V.

In all selections, the high or low effects of the alleles at the n loci are not limited to the selection antigen but may also influence the immune response to immunogens non-cross-reactive with the selection antigen. This multispecific effect is not general, as the difference in antibody response between H and L responder mice to various unrelated antigens may be identical, smaller, insignificant or even inverse as compared with the difference in response to the selection antigen. Comparison of the results obtained in the five selections indicates that the multispecific effect is large in selections I and III, intermediate in selections II and IV and restricted in selection V.

Selective breeding was also carried out for mitotic responsiveness of lymph node cells to in vitro stimulation by phytohemagglutinin (PHA). The selection limit was reached after ten generations, the realized heritability was 0.24, the low responsiveness was incompletely dominant, and the character was under the control of 10-19 independent loci. These H and L responder mice also displayed a similar difference in responsiveness to concanavalin A, in mixed lymphocyte reaction and graft-versus-host reaction, but produced the same antibody titer when immunized with SRBC.

Whether selective breeding for a polygenic character, such as antibody or mitotic responsiveness, also affects lifespan was investigated in selections I, II, III and PHA. The lifespan was longer in H than in L mice of selections I and II, but no difference was

Table 2 Antibody titers (log2) in H, L lines and interline hybrids of five selections

Mice

Selection 1 Mean± SD

Selection II Mean ± SD

Selection III Mean ± SD

Selection IV Mean ± SD

Selection V Mean + SD

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