Grant: Project Grant

B lymphocytes are the immune cells that produce proteins called antibodies that can neutralize bacteria and viruses. Our lab is interested in a molecule called "BAFF" which is a potent survival factor for B lymphocytes. Patients with rheumatoid arthritis, Sjogren's syndrome and Lupus have very high levels of BAFF in their serum, suggesting that excessive levels of BAFF may cause autoimmune disease. Likewise, mice that have been engineered to express high levels of BAFF have a surplus of B cells in their circulation and develop a curious kidney disease. We have examined BAFF over-expressing mice and found that a particular antibody class called IgA is abnormally trapped in the glomeruli of their kidneys. Concordant with this finding, we also observed that IgA levels were very high in the blood and in the gut, and when IgA is removed from these mice, kidney pathology does not occur. These data suggest that BAFF over-expressing mice may serve as a model for Berger's disease, also called IgA nephropathy. Patients with Berger's disease suffer from chronic kidney impairment, with many of these patients ultimately requiring dialysis or kidney transplantation. Our research takes advantage of BAFF over-expressing mice to study Berger's disease, since very little is known about how this disease evolves. Using various experimental approaches, we will test which immune cells are responsible for modulating the IgA disease we observe in BAFF over-expressing mice. We have also extended our experiments from this animal model to patient samples in order to validate our findings and to provide clues for how to treat Berger's disease, which is the most common form of glomerulonephritis worldwide.