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Biomedical subjects

D Mouton

Publications and source records attributed to D Mouton.

At least 73 records · Page 4Linked to original sources
PubMed1983

Inverse modification of antibody responsiveness to RGG in lines of mice selected for high or low responses to somatic antigen of Salmonella.

High (H/s) and low (L/s) antibody responder lines of mice selected according to their response to the somatic (s) antigen of Salmonella (Selection IV) have unexpected inverse capacity for antibody production to rabbit gamma globulin (RGG): H/s mice are low or even nonresponders to this antigen, whereas L/s mice are high responders. It was shown that the phenotypic variability within each line is due to environmental factors. RGG was a selection antigen in Selection V; the high (H/p) and low (L/p) responder mice are therefore considered as homozygous for the RGG genes. Responsiveness to RGG was investigated in F1 and F2 hybrids obtained by crossing the phenotypically similar RGG responder or nonresponder mice of Selections IV and V. The results support the hypothesis that the same genes control the response to RGG in L/s and H/p lines as well as in H/s and L/p lines. This means that the genes specific for RGG responsiveness were independent from those regulating responses to the s antigen. Unaffected by the selective breeding in Selection IV, they have been fixed by chance in an inverse way in H/s and L/s lines.

Animals↗
PubMed1982

[Relationship between red blood cell magnesium level and immune response in the mouse].

Red Blood cell (RBC) and plasma (P) Magnesium concentrations have been determined by atomic absorption spectrophotometry on male Mice belonging to various inbred strains: High and low responders and H-2 congenic. The antibody (Ab) levels have also been measured 10 days after injecting a threshold quantity of Sheep red cells. The strains with a high Ab response exhibit lower RBC Mg concentrations than those having a low response. Similar results, but less significant, are obtained for PMg. These findings confirm those previously obtained in Men. They suggest, moreover, the action of various genetic factors on this phenomenon, some of them being possibly associated with the major complex of histocompatibility.

Animals↗
PubMed1982

Evidence for distinct polygenic regulation of antibody responses to some unrelated antigens in lines of mice selected for high or low antibody responses to somatic antigen of Salmonella.

The effect of the selective breeding of mice for high or low antibody production to complex immunogens is largely "nonspecific", since it modifies the responsiveness of high (H) and low (L) lines to many antigens unrelated to the selection antigen. However, the nonspecific effect of the polygenic control operating in these lines is not a general feature. For example, the group of genes in selection IV, carried out for responsiveness to somatic antigen of Salmonella, does not modify the responses to sheep erythrocytes (SE). Despite equivalent responses in H and L mice of selection IV, a large variability was found in individual responses of F2 interline hybrids, which demonstrates the presence of alleles with high or low effect on responses to SE. A selective breeding (Selection IV-A) was therefore initiated from this F2 population for responsiveness to SE.A progressive interline divergence occurred during the first seven generations of selection; the interline separation was due to polygenic regulation (about four independent loci from a preliminary estimate). Equivalent responses to the s antigen of Salmonella are observed in the two lines. This constitutes additional evidence for distinct polygenic regulation of responses to SE and to somatic antigen. Moreover, the pattern of responses to several unrelated antigens (nonspecific effect) also differs between Selections IV and IV-A.

Animals↗
PubMed1982

Quantitative effect of H-2-linked gene(s) on antibody response to human gamma-globulin.

H-2-linked gene(s) have been found to play a role in the quantitative regulation of response to human gamma-globulin (HGG) in mice selected for high or low antibody responsiveness to sheep erythrocytes. Unexpectedly, in a random genetically heterogeneous population of F2 interline hybrids, the gene(s) linked to the H-2 phenotype of H mice has a "low" effect, and the gene(s) linked to the H-2 phenotype of L mice a "high" effect on the magnitude of antibody response to HGG. In H and L mice, the non-specific polygenic control of antibody responsiveness is able to compensate/counteract the inverse effect of HGG-specific H-2-linked gene(s) since the usual interline difference is observed.

Animals↗
PubMed1982

Genetic parameters of the polygenic regulation of antibody responsiveness to flagellar and somatic antigens of salmonellae.

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-reacting 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 fAg. 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 (less than 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 if 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 Salm. or. Ags. The H-2 effect accounts for 25% of the total interline difference.

Agglutinins↗
PubMed1982

Both genetic background and environmental factors modify the phenotypic expression of H-2 associated genes participating in the polygenic control of antibody responsiveness to Salmonella antigens.

The genetic control of responsiveness to flagellar (f) and somatic (s) antigens of Salmonellae was studied in high (H) and low (L) lines of mice selected for the character 'antibody response to sheep erythrocytes'. The minimal immunogenic dose was, for the two antigens, lower in H than in L mice and the dominance of the responder phenotype was then greater in F1 hybrid females than in males. Genes associated with H-2 locus intervene in the responses to each antigen. Their expression was found to vary according to the conditions of immunization and to the sex. The quantifiable H-2 effect was measured in interline hybrids, i.e. on an heterogeneous genetic background equivalent to that of F2. In the case of the flagellar (f) antigen, the H-2 locus was responsible in secondary response for about 50% of the interline difference in the two sexes. In the primary response, the H-2 effect was only observed in females. It was smaller (25% of the interline difference) and independent of the antigen dose. In contrast, with somatic (s) antigen the H-2 locus did not intervene in the control of secondary response. The H-2 effect in the primary response was again only found in females. Unexpectedly, the allele linked to the H-2 phenotype of L mice had a more favourable effect on hybrid responsiveness than that linked to the phenotype of H mice.

Animals↗
PubMed1979

Genetic analysis of antibody responsiveness to sheep erythrocytes in crosses between lines of mice selected for high or low antibody synthesis.

Two selective breedings of mice for minimal or maximal agglutinin response to heterologous erythrocytes were carried out (selection I and II). Preliminary reported data indicated that for both selections the heritability was between 0.18 and 0.36 and the number of relevant loci from 7--13. The results reported in this article are definitive since the data of ten to twenty generations at selection limit are available and large populations of interline hybrids F1, F2 and both backcrosses were analysed. The character 'high response' was partially dominant in F1 hybrids of both selections, the degree of this incomplete dominance was 0.27 in selection I and 0.54 in selection II. In selection I, 38% of the F2 variance was due to genetic factors (VG) and 62% to environmental effects (VE). The partition of phenotypic variance of F2 and backcrosses into additive variance (VA) and dominance variance (VD) was made according to three methods and the mean results were: VA = 0.72 and VD = 0.05. The resulting mean heritability was 0.35 and the number of relevant loci about ten. In selection II, 69% of the F2 variance was due to VG and 31% to VE. The three methods of variance calculation give somewhat discordant results. According to the more probable estimation (see discussion) VA = 0.95, the mean heritability was 0.23 and the number of loci, about 6. The results obtained in crosses between homologous lines of the two selections indicate that the two 'high' lines have probably identical homogeneous genetic constitution while the two 'low' lines contain some different 'high' effect loci.

Agglutinins↗
PubMed1976

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

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.

Animals↗
PubMed1976

Genetic regulation of macrophage functions.

Normal phagocytic function is genetically determined but maintained in a rather narrow range of variation. Phagocytosis stimulation induced by different agents is variable according to species, strains or individuals. Variation is environmental, to a great extent, but has also a genetic component which differs in each case. Selective breeding for macrophage responsiveness to triolein stimulation was successful. However, the relevant genes have only a small effect on antibody synthesis. Macrophages of mice selected for high and low antibody synthesis have a similar phagocytic function but their capacities of antigen processing are quite different.

Animals↗
PubMed1975

Genetic control of macrophage functions. I. Polygenic regulation of phagocytosis stimulation produced by Glyceryl Trioleate.

The phagocytic index K, established from the rate of blood clearance of colloidal carbon, measures the phagocytic activity of RE macrophages in contact with the circulating blood. The intravenous injection of glyceryl trioleate (triolein) produces a marked stimulation of the phagocytic activity of RE macrophages. This response is higher in the female than in the male mice. The phenotypic character "responsiveness of macrophage to triolein" presents large individual variants in population of random bred albinos mice. This character is submitted to polygenic regulation. Starting from a foundation population of 25 males and 25 females random bred albinos, mice, two lines were separated by selective breeding for the character "responsiveness to triolein": a "high" responder line, KTH, and a "low" responder line, KTL. After 26 consecutive generations of selective breeding, KTH mice present a very high response to triolein while KTL mice are almost irresponsive. The heritability of this character (h2) calculated from the interline divergence is of 12% plus or minus 1. This value of h2 indicates that the character investigated is determined by the cumulative effect of a group of about 27 independently segregating loci. The distribution of the character in (KTH plus KTL)F1 and their backcrosses with parental lines suggests that low responsiveness is dominant over high responsiveness. The genetic regulation of responsiveness to triolein is independent from the dose administered. These results are discussed in relation to the importance of genetic factors controlling macrophage functions involved in lipid metabolism and in the specific mechanisms of immunity.

Animals↗
PubMed1972

Genetic factors controlling anti-sheep erythrocyte antibody response and immunoglobulin synthesis in backcross and F2 progeny of mice genetically selected for "high" or "low" antibody synthesis.

Agglutinin responses to sheep erythrocytes and immunoglobulin heavy chain phenotypes determined in F(1), F(2), and backcross progeny of mice genetically selected for high and low antibody synthesis indicated that an immune response gene for sheep erythrocytes is linked to the immunoglobulin heavy chain allotype. Mice homozygous for the phenotype of the high line had significantly higher titers than mice homozygous for the phenotype of the low line. An association was also observed in some progeny of the backcross of the F(1) generation with the low line. However, the control of the immune response was clearly multigenic since heterozygous mice of the same phenotype (2/3, 5) resulting from the two backcrosses (high and low) had very different immune responses. Immunoglobulin levels in the same progeny showed no linkage to the immunoglobulin allotype but a rather simple pattern of inheritance.

Animals↗
PubMed1972

Cytodynamics of the immune response in two lines of mice genetically selected for "high" and "low" antibody synthesis.

Two lines of mice have been separated by selective breeding for the character "agglutinin production to heterologous erythrocytes." Around the 18th generation of selection the two lines could be considered as homozygous for the character investigated. This trait is under the control of a group of additive genes. The interline difference in the production of anti-SE agglutinins was verified for the range of antigen doses from subimmunogenic to maximal. After intravenous immunization with an optimal dose of SE, the duration of the exponential rise in serum antibody was 4-5 days in both lines. At this time most of the interline difference in responsiveness is already expressed. A cytodynamic study carried out in terms of plaque-forming cells (PFC) and rosette-forming cells (RFC) in the spleen during the exponential phase showed that the principal interline difference is found in the doubling time of cells engaged in the immune response. More precise cytodynamic analysis made in terms of RFC showed that the doubling time of RFC is 9 hr in high responder and 16 hr in low responder mice. The duration of the exponential rise and the number of target cells stimulated by antigen is the same in both lines. The interline difference at the end of the exponential rise (4 days postimmunization) is larger in terms of serum antibody (30-40-fold) than in terms of PFC or RFC (20- and 11-fold, respectively). A morphological study of RFC in nonimmunized mice showed that about 90% of rosettes were formed by small lymphocytes in both lines. The remainder were medium-sized lymphocytes. At the peak of the cellular response the RFC have differentiated into large lymphocytes, blast cells, and plasma cells. The contribution of plasma cells to RFC is much greater in the high than in the low line. The cytodynamic and morphologic results presented in this article are compatible with the hypothesis that the group of genes segregated in each line during the selective breeding control and regulate the rate of multiplication and differentiation of the antibody-producing cells.

Agglutination Tests↗