Features such as, latent allotype expression, imbalances in the expression of allelic products in heterozygous animals, allotype suppression, and allelic selection, provide evidence that the phenotypic expression of Ig genes is highly regulated. Due to the absence of the appropriate experimental system, the molecular mechanism((s) acting at the DNA level which regulate the expression of Ig genes in a manner that is consistent with these features of Ig allotype expression are not yet understood. The rabbit Ig K group b allotypes provide a valuable model with which to study the regulated expression of Ig genes. This system has not been exploited in molecular biological studies at the DNA level due to the absence in the rabbit of a reproducing source of expressed allotype-defined Ig genes. This difficulty has been circumvented by the formation of rabbit-mouse hybridomas (RMH). The long-term objective of the project is to employ these cells lines as a means to develop the rabbit Ig K group b allotype system into an experimental model with which to examine at the DNA level mechanisms which regulate the expression of Ig genes encoding specific allotypes. As an initial step in the development of this system, the allotype-defined rabbit Ig K genes will be isolated from the RMH cell lines 12F2 and H158. The former hybridoma secretes a monoclonal rabbit Ig K L chain of b4 allotype, while the latter produces a monoclonal rabbit Ig K chain of b6 allotype. During the course of the project, mechanisms involved in the formation of a functional rabbit VK gene will be examined. The isolated rabbit b4 and b6 K genes will be examined in future studies designed to 1) locate and define sequences, and mechanisms, involved in the regulated expression of these allotype-defined Ig K gene loci; 2) provide DNA probes with which to determine the overall structure of the expressed b4 and b6 K gene loci present within the genome of the corresponding RMH cell line. Regulation of Ig allotype expression has been shown to be involved in a regulatory system which influences antibody responses to various antigens. In addition, latent allotype expression has been observed in allelic products encoded by the major histo-compatibility complex. Products encoded by this gene locus are intimately involved in immune function and allograft rejection. In light of these findings, the research outlined in the proposed project could have implications which extend beyond the regulated expression of rabbit Ig genes.
| Ishaq, M; Wolf, B; Dreher, K (1990) cDNA sequences encoding rabbit latent kappa 1 b5 and b6 Ig L chains. J Immunol 145:3463-7 |
| Dreher, K L; Asundi, V; Wolf, B et al. (1990) Rabbit Ig kappa 1b6 gene structure. J Immunol 145:325-30 |
