2001 B Cells
Some B cells, which normally lie dormant, are programmed to produce self-destructive antibodies (autoantibodies). These cells are turned on in people with lupus.
Dr. Vilen’s research asked if newly recognized proteins may be how the off-switch is overridden in lupus, and whether there may be treatment options that reverse this process.
With LRI funding for her novel idea, Dr. Vilen specifically pursued the question as to whether antigens from apoptotic cells are displayed on the surface of other immune cells to B cells, and whether this might provide a sufficiently strong activating signal to trigger autoantibody production.
Her major discoveries have shed light on the regulation of B cells in lupus, and in addition to publishing her work she has presented her research at two prestigious Keystone conferences (2004 and 2005), and has been invited to give seminars across the country.
“The research we initiated with the LRI award has identified how autoreactive B cells are regulated during innate immune responses….Clearly, the tolerance mechanisms that silence autoreactive cells must be powerful. Identifying them and understanding their dysregulation is of significant impact in lupus research,” said Dr. Vilen.
“Before my LRI award my research focused on B cell signaling and tolerance. The LRI award was instrumental in changing that focus toward disease and dysregulation of B cell responses. We continue to study SLE as our primary focus with all members of my laboratory (4 students and 2 post-docs) engaged in lupus-related research.” – Dr. Barbara Vilen, 2010
Low-affinity, Smith antigen-specific B cells are tolerized by dendritic cells and macrophages. Kilmon MA, Rutan JA, Clarke SH, Vilen BJ. J Immunol. 2005 Jul 1;175(1):37-41.
Dendritic cells from lupus-prone mice are defective in repressing autoreactive B cells. Gilbert, M.R., D.G. Carnathan, P.C. Cogswell, A.S. Baldwin Jr., B.J. Vilen. J Immunol. 2007 178:4803-4810.
Macrophages prevent the differentiation of autoreactive B cells by secreting CD40 ligand and IL-6. Kilmon M.A., N.J. Wagner, A. Garland, K. Aviszus, L. Wysoki, and B.J. Vilen. Blood 2007 110:1595-1602.
Dr. Vilen has received two major NIH-funded awards to continue the research she began with her LRI funding. In 2003, she was awarded a 5-year NIH grant of $1,012.500 in direct costs ($1,627,000 including indirect costs). In 2008 she was awarded a 4-year, $1 million grant to examine the role of dendritic cells and macrophages in lupus. She also has funding in the amount of $200,000 through the Arthritis Foundation, and has a patent application pending.
Rev. July 2010