The central focus of the proposed research is to determine the genetic and regulatory influences determining the quantity and quality of antibody produced in an immune response. In particular, we are examining the response to a defined hapten by inbred mice. We have characterized the genes controlling expression of antibody bearing a particular idiotype, an antigenic determinant borne by anti-2,4-dinitrophenyl (DNP) antibody in certain strains of inbred mice. Genes encoding the variable regions of both light and heavy immunoglobulin polypeptide chains are involved in the expression of this idiotype. Secondly, we have determined the kinetics of idiotype of expression. The idiotype is transiently dominant during secondary antibody responses. Third, we have examined the question of whether this regulation of idiotype can also account for the regulation of the expression of different constant region of immunoglobulin gene products. Our results suggest that the regulation of constant region gene expression is an independent process from the regulation of variable region gene products. Finally, we have sought an explanation of the reason for preferential expression of this particular idiotype. We have found that the idiotype is found in significant amounts in normal serum, but in that form does not bind the antigen DNP. We have prepared such idiotype positive, non-DNP binding material as a monoclonal antibody in order to determine the antigens which induce its expression. It is our hypothesis that this idiotypic material activates a set of idiotype-specific helper T cells, which in turn activate DNP-specific, idiotypic B cells also activated by conventional helper T cells. We are currently testing this hypothesis.
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