The Role of bHLH Proteins in Human Lymphopoiesis

Two laboratories are combining effort in this subproject to learn how helix-loop-helix (HLH) proteins and the Id family of transcriptional repressors coordinately regulate human lymphocyte formation. Animal studies indicate that critical steps in immune system development depend on precisely controlled levels of these proteins.  Furthermore, these transcription factors may intersect with intracellular signals delivered via the Notch family of proteins.  Some observations indicate that there may be substantial species differences in mechanisms for lymphocyte formation.  Therefore, a new culture model, as well as a new xenograft system are being exploited to extend these observations to human cells.  Recent results confirm the validity of those experimental systems.  Descriptive information is now being collected about expression of the corresponding Notch, HLH and Id genes in carefully defined subsets of bone marrow precursors. In parallel, retroviral vectors constructs are being prepared to experimentally manipulate HLH activity in human hematopoietic cells.   Work conducted during the first year reinforced the feasibility of the original research plan and provided options for broadening the scope of the studies as needed.