Date of Award
Doctor of Philosophy (PhD)
The antibody response to Group A streptococcal carbohydrate was measured in 10 inbred mouse strains after immunization with whole heatkilled streptococcal vaccine. Using A/J and SWR/J mice, dose response studies were performed to determine optimai immunization conditions of dose, route of injection, and age of mice. In the course of these studies, inbred strains were identified which produced high and low levels of anti-Group A antibody after immunization with Group A vaccine. Subsequent genetic experiments demonstrated that the differences in antibody titer observed among some of these strains were under the genetic control of genes at several loci. When A/J and SWR/J mice are optimally immunized, they often produce high titers of anti-Group A antibody (antibody concentrations ranging from 5 to 15 mg/ml in SWR/J mice and from 5 to 60 mg/ml in A/J mice) with restricted heterogeneity. The restriction of heterogeneity of the anti-Group A antibody in these sera has been documented by microzone electrophoresis of isolated antibodies and by disc gel electrophoresis of reduced and alkylated anti-Group A antibody. Mice with this type of monodisperse anti-Group A antibody have been used as donors for spleen cell transfers (107 spleen cells per recipient) to irradiated (500 R) recipient syngeneic mice. The immunized recipient mice produced anti-Group A antibody identical to that of the donor mouse. Such cell transfer lines have been propagated for as many as three passages. Antibodies isolated from the original donor, or from one of the recipients of such spleen cell transfer lines, have been used to prepare anti-idiotypic sera in rabbits. Idiotypy was detected by passive hemagglutination inhibition and by the radio-immune 'tube binding assay. One of the idiotypes studies was found to be present in SWR/J anti-Group A antibody and generally absent from anti-Group A antibody produced by A/J mice. It has been possible to demonstrate the inheritance of this idiotypic marker in hybrid A/J x SWR/J and in A/J x (A/J x SWR/J) backcross mice. The pattern of inheritance that was observed is consistent with a small number of loci, possibly only one, controlling the inheritance of idiotypic determinants.
Briles, David Elwood, "Studies on the Inheritance of Idiotypic Markers of Mouse Antibody to Streptococcal Group A Carbohydrate and on Other Genetic Factors Which Influence the Immune Response" (1973). Student Theses and Dissertations. 538.