Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis

Abstract

Selective breeding for the character "agglutinin production to heterologous erythrocytes" was performed on random-bred populations of albino mice. Two types of selection were carried out: Selection I: the first 6 generations were immunized with sheep erythrocytes (SE), then SE and pigeon erythrocytes (PE) were alternated at each generation to avoid the interference of maternal antibody. Selection II: all generations were immunized with SE 60-70 days after weaning in order to eliminate the maternal antibody. Both were selected for the character agglutinin titer 14 days after immunization using an optimal dose of erythrocytes. Selection I. The mean response to SE of the foundation population was 7.36 +/- 1.60. The selection limit was attained between the 15th and the 20th generation. The F20--F30 were considered as homozygous for the character investigated. The mean SE agglutinin titers were 9.15 (1/2820) in the high responder line and 2 (1/20) in the low responder line. This corresponds to 140-fold interline difference in agglutinin titers. SE agglutinins determined in F1 hybrids, F2 hybrids and backcrosses obtained from F23--F29 demonstrated incomplete dominance of high responsiveness (23-29%). The inbreeding coefficient produced by close colony breeding was 0.55 in high and 0.71 in low responders at the 20th generation when both lines were homozygous with respect to agglutinin synthesis. Selection II. The mean response of the foundation population to SE was 7.79 +/- 1.56. The selection limit was attained in F14--F17 generations that were considered homozygous for the character investigated. The mean SE agglutinin titer was 9.2 (1/2900) in high responders and 2.8 (1/35) in low responders, which is an 83-fold interline difference in agglutinin titers. The results of both selections indicate that the character agglutinin synthesis is subject to polygenic regulation. The heritability (h2) of this character was estimated to be between 0.18 and 0.36 (range between the extreme values of Selections I and II.

Toward genetic dissection of high and low antibody responsiveness in Biozzi mice

“…The finding that the six identified QTLs accounted for about 40% of the overall phenotypic variance in BcL1, without evidence for a major gene effect, fits with our previous estimate of genetic versus environmental variance partition in (HϫL) segregant hybrids (6). This indicates that most of the Im genes contributing to H͞L difference were presumably detected.…”

“…The production of high (H) and low (L) Ab responder lines of mice by selective breeding for Ab production to heterologous erythrocytes has opened the way to investigate the multigenic control of quantitative Ab responses (5). It was estimated that 10 independently segregating loci endowed with additive effects are responsible for the huge (240-fold) multispecific difference separating H and L Ab titer phenotypes (6). Recently, a genome-wide search for the mapping of the relevant genes was undertaken; the genotyping for 90 informative microsatellite markers was restricted to the mice giving the highest and lowest Ab responses among a large immunized (HϫL)F 2 population (7).…”

“…Such an evaluation of the QTL effect on parameters with continuous variation has already been reported in several animal models (12)(13)(14)(15)(16)(17). We chose to study a backcross to L line because of the partial dominance of high-over-low anti-sheep red blood cell (SRBC) responses (6), with the risk, however, of an impaired detection of any gene having an opposite dominance direction.…”

Defective antigen presentation by macrophages from mice genetically selected for low antibody response

“…The selective breeding affected not only the antibody response to xenogeneic erythrocytes, but also the responses to many other immunogens, unrelated to the selection antigens, such as hemocyanin [2], bovine serum albumin [3], type 3 pneumococcal polysaccharide [4], trinitrophenylated lipopolysaccharide [5], T4 bacteriophage [6] and histocompatibility antigens [7]. This regulation of the antibody response is controlled by about 10 independent loci, one of which is H-Zlinked, when antigen is administered at the optimal immunizing dose [8].…”

Immune Response to the Rhodococcus equi Infection in High and Low Antibody‐Producing Mice (Selection IV‐A)

“…These lines were produced by bidirectional selective breeding of High and Low responder lines of mice to natural multideterminant immunogens administered at optimal doses. The different antigens used were sheep erythrocytes (SE) and pigeon erythrocytes (Selection I) (4), SE only (Selection II) (15), flagellar and somatic antigens of Salmonella sp. (Selections III and IV, respectively) (40), bovine serum albumin, and rabbit γ-globulin (Selection V) (33).…”