Biomedical subjects
Publications and source records attributed to D Mouton.
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The injection of aggregate-free or tolerogenic human gamma globulin (t-HGG) induced tolerance in two lines of mice selected for high or low antibody responsiveness (high responder (H) or low responder (L) lines, respectively). In L mice, the tolerance state was very short and could no longer be obtained when the challenge injection was delayed for four weeks after tolerogenic treatment. At that time, an antibody response to t-HGG was observed in both lines; in H mice, however, this was followed by a partial tolerance state. These results and those previously obtained concerning tolerance induction to bovine serum albumin and rabbit gamma globulin in H and L mice suggest at least partial independent genetic control of antibody responsiveness and susceptibility to tolerance induction.
Five selective breedings have been performed for the character "antibody production" in mice. Two of them, Selection I and Selection II, carried out for maximal (H) and minimal (L) antibody response to heterologous erythrocytes, gave similar results concerning the genetic parameters and the extent of modification of antibody response to unrelated antigens (non-specific effect of the selection). Macrophage characteristics and the expression of T-mediated immunity were investigated in H and L mice of Selection II and compared with results already obtained in Selection I. The phagocytic activity of macrophages was similar in the two lines, whereas an important interline difference was observed concerning the persistence of the immunogen, which was much shorter in L than in H mice. The more rapid antigen catabolism in L mice explains why the threshold immunogenic dose was higher in these mice and why the antibody response was much more improved in L than in H mice by repeated antigen administration. Results on skin allograft rejection, delayed-type hypersensitivity and responsiveness to T mitogen demonstrated that H and L mice have a similar ability to mount T-mediated immunity reactions. Two findings obtained in Selection I were therefore confirmed: 1) macrophage catabolic activity is modified by selection in the opposite direction of antibody production: low antibody responsiveness is associated with high macrophage activity and vice-versa; 2) and the expression of cell-mediated immunity and of the humoral immune response are at least partially under independent genetic regulation.
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The genetic control of IgE- and HA-antibody responses to ovalbumin (OV) was investigated in H and L antibody responder lines of mice and in their hybrids. After immunization with threshold doses of OV (0.5 and 0.05 microgram OV) H mice were responder in terms of both HA and IgE antibody whereas L mice were non-responder. This trait was under monogenic control and the relevant gene was H-2-linked. The dominance direction depended on the antigen dose since high response was dominant for 0.5 microgram and recessive for 0.05 microgram. After immunization with a higher dose (10 microgram OV), the intervention of non-H-2 genes in the genetic control of the antibody response becomes manifest. The quantitative effect of the H-2 locus was greater for IgE- than for HA-antibody response, suggesting a less complex genetic control at the IgE-antibody level.
Immune responses depend upon the dose of antigen and the line of mice. Threshold doses of antigen are lower in HL, higher in LL and intermediate in hybrids. The responses obtained in F1, F2 and backcrosses demonstrate the genetic control of the interline difference. The correlation between IgE and hemagglutinating antibodies responses suggests a common genetic control for the synthesis of the two types of antibodies.
Four two-way genetic selections of outbred mice for the quantitative character "agglutinin production" to heterologous erythrocytes and flagellar or somatic antigens of Salmonella are briefly described. The principal genetic parameters regulating the quantitative antibody response are the following: 1) the character is polygenic; the number of independent loci is estimated between 7 and 16; 2) the heritability of the character (h2) is comprised between 0.17 and 0.21; 3) the maximal interline separation RT (4.8-7.8 log2) is reached after about 15 consecutive generations of selective breeding; (4) the rate of interline separation/generation RG is 0.32-0.48 log2. 5) The phenotypic variance V(P) of the foundation populations is due for 52%-63% to genetic factors V(G) and for 37%-48% to environmental factors V(E); 6) The effect of the selective breeding is essentially non-specific; it modifies the antibody responsiveness to many unrelated complex immunogens.