Genetic Parameters of the Polygenic Regulation of Antibody Responsiveness to Flagellar and Somatic Antigens of Salmonellae

Abstract

Summary Selective breedings of mice were carried out for quantitative antibody responsiveness to flagellar Ag., f (Selection III) or somatic Ag., s (Selection IV) of two non cross‐reaction Salmonellae (Salm. tm., Salm. or.) alternated for immunization of consecutive generations. At the selection limit, these selections produced homozygous high (H) and low (L) responder lines for the character investigated: peak agglutinin response to optimal secondary immunization. The responsiveness to both f and s Ags. is submitted to polygenic regulation. The heritability (h2) realized during the selective breeding was 0.37 ± 0.07 for the response to f Ag. and 0.40 ± 0.1 for the response to s Ag. The respective part of genetic and environmental variance in F2 hybrids was 64% and 36% in selection III and 61% and 39% in selection IV. In the two selections, the dominance variance is negligible (<1%), therefore the genetic variance is essentially additive. The additive variance calculated as the heritable fraction of the F2 hybrid variance is somewhat lower, the reason for this difference is discussed. The quantitative antibody response to f Ag. in selection III is controlled by about seven independent loci. The antibody response to s Ag. in selection IV is controlled by about four independent loci. A possible association of relevant genes with the H‐2 locus was investigated. In selection III, no significant participation of H‐2 linked genes, in the regulation of responses to f and s Ags. of Salm, tm and Salm. or. could be demonstrated. In selection IV a partial contribution of H‐2 linked genes was observed concerning responsiveness to both f and s Ags. of Salm. tm.. but not to Salm. or. Ags. The H‐2 effect accounts for 25% of the total interline difference.

Host and Bacterial Factors Affecting Induction of Immune Responses to Flagellin Expressed by AttenuatedSalmonellaVaccine Strains

“…In an attempt to evaluate (4,37). Originally derived from Swiss albino mice, such mouse lines are considered homozygous for the relevant alleles involved with the generation of antibody responses, which are considered to comprise 4 to 10 independently segregating loci responsible for the interline differences (35). As expected, high-and low-level responders showed distinct immunological behaviors toward type d flagellin after the administration of attenuated S. enterica serovar Dublin strains via mucosal and parenteral routes.…”

Human IgG but not IgM Antibodies can Protect Mice from the Challenge with Live O6 Escherichia coli

“…Inbred male HIII (high III) mice, 6-8 weeks old (kindly donated by Dr Maria Siqueira, Butantan Institute, São Paulo, Brazil), selected for high susceptibility to infection with Salmonella typhimurium [5][6][7] were used. The HIII selection of mice began in 1976, made by Dr Maria Siqueira as an outbred selection for high susceptibility to S. typhimurium infection [6]. In 1997, the inbreeding process began, and after 14 generations, the HIII mice were transferred to an isolator, where the inbreeding process continued.…”

“…This phenotype was shown to be controlled by approximately seven independent loci [6] expressing themselves at several distinct cellular levels [6]. High (HIII) antibody-responder line was submitted to 20 inbreeding generations in order to increase intraline homogeneity at the levels of polymorphism markers [7].…”

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

“…3)] than the 0.2 value constantly observed in the original selections [2]. As discussed elsewhere [9] there is in fact an underevaluation of h2 in the original selection since the calculation of cumulated S is more affected by environmental error than that of R. This has been established in selections I11 and IV in which the antibody responses to both f and s Ags of Salmonella were measured. In these two selections, the interline divergence for the two Ags was strictly parallel but the h2 value was significantly higher (0.37-0.40) when calculated for the so called "associated Ag" since the bias on S value was lessened.…”