Collaborative Project: Molecular Cloning of mRNA Encoding Latent Ig Allotypes
{'Code': '08060200', 'Directorate': {'LongName': 'Direct For Biological Sciences'}, 'Division': {'LongName': 'Division of Cellular Biosciences'}}
{'SignBlockName': 'Maryanna P. Henkart'}
In the rabbit, most immunoglobulin (Ig) nominal allotypes are presumed to be inherited via codominant allelic segregation. However, latent or non-allelic gene activation has been documented for the Ig kappa light and gamma heavy chain gene loci. Serological and structural analyses have confirmed the existence of these latent Ig allotypes. Molecular mechanisms acting at the nucleic acid level which allow the expression of latent allotypes have yet to be determined. A major obstacle in studying the expression of latent Ig allotypes has been the inability reproducibly to induce the expression of latent Ig molecules. This obstacle has been circumvented by antigenic stimulation using Trypanosoma brucei to induce the expression of latent Ig kappa light and gamma heavy chain sequences in the rabbit. Lymph nodes taken from infected rabbits have been shown to contain poly (A) positive RNA sequences encoding latent kappa light and gamma heavy chain allotypes. This represents the first time latent allotypes have been detected at the nucleic acid level. The long term objective of this investigation is to elucidate molecular and cellular mechanisms which generate the expression of nucleic acid sequences encoding latent Ig allotypes. To achieve this the following specific aims will be pursued: Isolation and structural analysis of poly (A)-positive RNA sequences encoding: 1) latent b5 and b6 kappa lightchains, 2) the latent a1-e14 haplotype, 3) the nominal b6 kappalight chain secreted by the rabbit-mouse hybridoma cell line, H158. Isolation of these RNA sequences will be achieved by employing standard duplex cDNA cloning technology and novel allotype-specific screening methodologies. Isolation of cDNA sequences encoding latent Ig allotypes will verify their existence at the nucleic acid level and allow direct structural comparisons to be made with their nominal allotypic counterparts. Information obtained will be used in future studies designed to isolate the actively transcribed Ig kappa and gamma genes encoding these latent sequences. These studies will contribute to our overall understanding of the regulation of Ig gene expression.
{'FirstName': 'Kevin', 'LastName': 'Dreher', 'EmailAddress': None, 'StartDate': '08/15/1987', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Weis Center for Research', 'CityName': 'Danville', 'ZipCode': '17822', 'PhoneNumber': '7172718663', 'StreetAddress': 'Geisinger Clinic', 'CountryName': 'United States', 'StateName': 'Pennsylvania', 'StateCode': 'PA'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8717426.xml'}