chanisms involved in the regulation of isotype switching to IgA and the subsequent turation of IgA expressing cells to IgA secreting cells. Effective invnunization against teric pathogens is correlated with the ability to mount an IgA response. Although HIV n gain entrance to the host via a gastrointestinal route, it is unclear at this point an IgA response is protective or if it exacerbates the disease process. Regardless, understanding of the regulation of IgA responses could aid in the design of vaccines ainst a wide variety of pathogens that enter the host via mucosal/enteric routes. In ntrast, an IgA response could have deleterious effects in inflammatory bowel disease by imulating eosinophil degranulation.
The specific aims of the proposal are to study the ocess of isotype switching to IgA by investigating transcriptional regulation of rmline a MRNA transcripts that appear to be the first step in isotype switching to IgA. e goals are to determine if germline a MRNA transcripts commit a B cell to switch to A, the requirements for the induction of germline a MRNA, the relative roles of message ability and rate of transcription in achieving the steady state level of germline a NA, and to identify a functional promoter for these transcripts. To accomplish these als, the germline et transcripts will be cloned and a variety of techniques including in hybridization and nuclear run-on transcription will be employed to study their gulation. Gene transfer experiments will be used to identify a functional promoter. second aspect of the development of an IgA response is the regulation of maturation of A expressing cells to IgA secreting cells. In this respect, the specific aims of this udy are to determine the changes on a MRNA transcription that accompany the development f IgA memory cells to IgA secreting cells and to determine the role of transcription rmination on the choice of 3' terminus for a MRNA. To accomplish these goals, we will se a combination of S nuclease mapping to study changes in a MRNA transcription and uclear run-on assays to study transcription termination.
| Lebman, D A; Park, M J; Hansen-Bundy, S et al. (1994) Mechanism for transforming growth factor beta regulation of alpha mRNA in lipopolysaccharide-stimulated B cells. Int Immunol 6:113-9 |
| Lebman, D A; Park, M J; Fatica, R et al. (1992) Regulation of usage of membrane and secreted 3' termini of alpha mRNA differs from mu mRNA. J Immunol 148:3282-9 |
