Genetic regulation of multispecific antibody responsiveness: improvement of “high” and “low” characters

Abstract

The five selections carried out in the mouse for high or low antibody responsiveness to various multideterminant immunogens were successful. In all cases the large interline difference was shown to result from the additive effects of several independently segregating loci (polygenic regulation). However, important peculiarities were demonstrated in these original selections concerning either the cellular mechanisms operating or the effect of the selected genes on antibody responses to antigens unrelated with those used for the selection (multi-specific effect). In an attempt to improve and generalize the effect of selection, the 5 high and the 5 low lines were inter-crossed to obtain populations with a balanced proportion of the 5 genomes. These two populations were then submitted to selective breedings in which the phenotypic character was the weighted responses to pluri-antigen immunization. The data obtained in 16 consecutive generations of two selective breedings (general-primary, GP and general-secondary, GS, responses) carried out from these populations are reported. The genetic parameters of the response to GP and GS selections are compared with those obtained in the original selections. The final result of both GP and GS selections demonstrate a marked improvement of the high and low antibody production traits, both quantitatively (interline divergence) and qualitatively (multi-specific effect). The success of GP and GS selections agrees with the concept that distinct groups of genes are preferentially affected by selection according to the nature of the selection antigen and the immunization procedure.

Polymorphism ofTcrb andTcrg genes in Biozzi mice: Segregation analysis of a newTcrg haplotype with antibody responsiveness

“…Selection I was run on the response to sheep red blood cells (SRBC) and pigeon RBC and selection II on the response to SRBC alone. Selection GS was more recently obtained on the basis of weighted responses to multi-antigen immunization (Mouton et al 1988) and resulted in amplified interline divergence. In these three selections, H and L difference in antibody production is largely independent of antigen specificifies (multi-specific effect) and antibody isotypes.…”

“…This observation is consistent with the results in L-GS animals in which the Tcrg haplotype is not fixed. Mice of the GS selection included in this study are from the F20 generation (Mouton et al 1988). Considering that interline difference could not be improved from generation Ft8 to F20, H-GS and L-GS mice are probably homozygous at loci involved in the character under selection but not at irrelevant loci, since consanguinity has been avoided as far as possible during selective breeding.…”

Novel Immunogenic Epitopes in the NaPi-IIb Protein: Production of Monospecific Antibodies Using Synthetic Peptides Outlined on Isoform Specific Regions of the Type IIb Sodium-Dependent Phosphate Transporter (NaPi-IIb)

“…High III mice are a genetically selected strain that is well-known for its superior capacity to produce circulating antibodies, and this is preferable [41].…”

“…High III strain female mice [41], which were 2 months of age and weighed 18 -22 g, were obtained from the Immunogenetics Laboratory, Butantan Institute, SP, Brazil. All experimental procedures involving the animals were in accordance with the ethical principles of animal research adopted by the Brazilian Society of Animal Science and the National Brazilian Legislation No.…”

Proteína de 18kDa de Mycobacterium leprae: um modelo de carregadora para vacinas de segunda geração

“…Foram feitas inoculações intraperitoneais em camundongos de ambos os sexos da linhagem HGP (Mouton et al, 1988), utilizando 3 ou 4 animais por grupo. As sangrias foram realizadas no plexo venoso retro-orbital e o soro obtido foi mantido a -20°C até a dosagem das imunoglobulinas (IgG e IgM) por ELISA.…”