This is an RO3 application to investigate a new protein discovered and characterized by the applicant, called deltaBAFF. DeltaBAFF is a novel splicing isoform of the B cell regulator BAFF, a TNF-family protein with powerful immunoregulatory effects. Over-expression of BAFF leads to excessive B cell accumulation, activation, autoantibodies, and lupus-like disease, whereas an absence of deltaBAFF causes peripheral B cell immunodeficiency. It is important to understand how the balance between BAFF-mediated B cell survival and autoimmunity is controlled. The idea that deltaBAFF plays a role in restraining the effects of BAFF and regulating B lymphocyte homeostasis will be tested. The effects of specifically altering the ratio of deltaBAFF to full-length BAFF expression in vivo by transgenesis will be tested. The effects of homomultimers or heteromultimers on membrane expression and biological function will be tested. The long-term goal of these studies is to understand B lymphocyte homeostasis. Understanding the function of deltaBAFF may provide clues to help us understand and cure autoimmune disease and B lymphoid cancer.
| Collins, Christopher E; Gavin, Amanda L; Migone, Thi-Sau et al. (2006) B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels. Arthritis Res Ther 8:R6 |
| Ait-Azzouzene, Djemel; Gavin, Amanda L; Skog, Patrick et al. (2006) Effect of cell:cell competition and BAFF expression on peripheral B cell tolerance and B-1 cell survival in transgenic mice expressing a low level of Igkappa-reactive macroself antigen. Eur J Immunol 36:985-96 |
| Gavin, Amanda L; Duong, Bao; Skog, Patrick et al. (2005) deltaBAFF, a splice isoform of BAFF, opposes full-length BAFF activity in vivo in transgenic mouse models. J Immunol 175:319-28 |
