Nonspecific genetic regulation of antibody responsiveness in the mouse

Abstract

Four lines of mice were produced by selective breeding for quantitative agglutinin responsiveness to flagellar (f) or somatic (s) antigens (Ags) of Salmonellae: high (H) or low (L) responder lines to fAg and H and L responder lines to sAg. The Salmonellae contained both f and sAgs, the Ag used to perform the selection was the Selection Ag and the other was the Associated Ag. The selective breeding produced a progressive interline separation with an equivalent effect for both Ags. After 15 generations (F15) the level of agglutinin response was about 60 times higher in H than in L responders. About 50% of the phenotypic variation of the character investigated is determined by a group of immune response genes, the rest is due to environmental factors. The nonspecific effect of this group of immune response genes was investigated by measuring the responses to three independent antigens: Sheep erythrocytes (SE), dinitrophenyl-conjugated human IgG (DNP-HGG) and bovine IgG (BGG). The selection for fAg response produced an equivalent modification in the respnsiveness to the Associated Ag (97%) and to BGG (130%). This nonspecific effect was smaller for responsiveness to SE and DNP-HGG, 58% and 41% of the Selection Ag response, respectively. The selection for sAg response produced a nonspecific modification of responsiveness of 94% for the Associated Ag of 74% for BGG and 63% for DNP-HGG. An important exception concerned SE to which an equal antibody response is produced in high and low lines of sAg selection.

Immune recognition of salivary proteins from the cattle tick Rhipicephalus microplus differs according to the genotype of the bovine host

“…Highly infested hosts receive large amounts of tick saliva, which contains many immunosupressants, including immunoglobulin-binding proteins, which are abundantly transcribed in salivary glands of the feeding male tick [32], coinciding with the appearance of the host’s acquired immune response. The genetic composition of hosts affects the nature of the antibody response, including levels of total immunoglobulins [33–37], the IgG subclasses recruited, and antibody specificities [33, 38]. On the other hand, ticks ingest large amounts of host immunoglobulins presenting antibody activity [39].…”

Salmonella typhimurium infection in high and low antibody responder mice: inverse correlation between antibody responsiveness and resistance to infection

“…In selections III and IV, based on responsiveness to S.tm. Ag [20], no modification of macrophage catabolic activity towards Ag could be found [12,13]. LII I and L w mice, though, were found more resistant than their H mice counterparts to S. tin.…”

“…H and L mice were from selections I, II and IV A, based on Ab responsiveness to heterologous erythrocytes [10,21] and from selections III and IV, based on Ab responses to S.tm. Ag [20]. Mice of both sexes were used at 2-4 months.…”

Trypanosoma cruziInfection in Genetically Selected Mouse Lines: Genetic Linkage with Quantitative Trait Locus Controlling Antibody Response

“…This bidirectional selective pressure resulted in the accumulation of alleles at multiple quantitative trait loci (QTLs) in each H and L line endowed with opposite modulatory effects on the various steps of antibody biosynthesis [27]. The differences in antibody responses between H III and L III lines are not restricted just to the selection immunogen but encompass a wide range of complex antigens, showing evidence for multispecific effects of the relevant genes [28, 29]. Genetic analyses indicated that 5–10 QTLs regulate the antibody production phenotype, and a QTL mapping experiment using microsatellite markers yielded three highly significant QTLs on chromosomes 3, 8, and 9 [30].…”