This award will support collaborative research in genetics between Dr. Janet Stavnezer, University of Massachusetts Medical School, and Dr. Eva Severinson, Department of Immunology, University of Stockholm, Sweden. The objective of the proposed project is to study the molecular basis of expression of "genomic" or "sterile" transcripts of unrearranged im munoglobin constant region genes. Such transcription has been demonstrated to be a prelude to immunoglobin class switching. The ability of B cells to switch from production of one class of im munoglobin (Ig) to another is essential to the immune system, since different classes of Ig perform different functions. This process of class switching is highly regulated, as different classes are expressed in response to different antigens and at different sites in the body. In this project, the investigators propose to study the regulation of production of sterile transcripts. After determining the initiation sites for germline transcription of certain constant region genes and determining their promoters, the investigators will attempt to identify and characterize the DNA.binding proteins that bind to the promoter and then to obtain evidence of the roles these protein play in the regulation of such transcription. Drs. Stavnezer and Severinson are leaders in the field of the analysis of class switching, the former in the molecular analysis of transcription and expression of constant region genes, and the latter in the study of the biological mechanisms of switching. The results of this research will make an important contribution to the understanding of the immune system.
