Researchers at the University of California, San Diego (UCSD) School of Medicine have found clues that might lead to better treatment of lupus, showing that the spleen is the likely source of cells that are the origin of the disease. Michael Karin, Ph.D., professor pharmacology in UCSDs Laboratory of Gene Regulation and Signal Transduction, led the study to be published on line September 14 in advance of publication in the September issue of the journal Immunity.
The researchers worked with transgenic mouse models that were engineered to overproduce a special cytokine a hormone which regulates immunity called BAFF, a B-cell activating factor that is elevated in patients with lupus and other autoimmune diseases. The B cells are responsible for the production of antibodies in the body. Mice overproducing BAFF develop systemic lupus erythematosis (SLE)-like disease, very similar to human lupus, which is estimated to affect one in a thousand Americans, 90 percent of them women.
The research study showed that that a compartment of the spleen called the marginal zone is where the majority of autoreactive B cells are found. The scientists transplanted immune cells from the spleen's marginal zone in the mice with lupus into mice without their own B cells, and found that they immediately gave rise to pathogenic antibodies.
When the enlarged marginal zone cell pool in the mouse model was removed or reduced, the disease was prevented or strongly diminished.
"The study proved without a doubt that the transplanted B cells were the source of lupus auto-antibodies," said Gregg Silverman, M.D. professor of medicine in UCSDs Translational Oncology Program and contributor to the paper. "Identifying the spleens marginal zone as the likely source of these tissue-damaging antibodies gives us important insights into the cause of lupus as well as a target for new therapies."
The researchers also studied B-cell activation in two signalling pathways,
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
14-Sep-2006