Associate Medical Professor
Dr. Linda Spatz is interested in understanding how anti-double stranded (anti-dsDNA) antibodies which are the hallmark of the autoimmune disease Systemic Lupus Erythematosus (SLE), arise. Her laboratory is studying the regulation of anti-dsDNA B-cells. Normally these B cells are kept from secreting transgenic anti-ds DNA antibodies by regulatory mechanisms, collectively known as B cell tolerance. When one or more of these regulatory mechanisms goes awry, a breakdown in tolerance ensues and anti-dsDNA antibodies are secreted at elevated levels. These antibodies can deposit in various organs of the body including the skin, joints, and kidney where they can induce tissue damage. Dr. Spatz's laboratory is investigating potential genetic and environmental factors that can lead to a breakdown in anti-dsDNA B cell tolerance. Using an anti-dsDNA transgenic mouse model she is currently studying how the overexpression of a B cell survival factor known as BAFF, can lead to the loss of B cell tolerance and the secretion of transgenic anti-dsDNA antibodies.
In addition, Dr. Spatz is working in collaboration with Dr. Paul Gottlieb to study the role of the Epstein Barr virus (EBV) in the etiology of SLE. They have observed that immunization of mice with a major nuclear protein of EBV known as EBNA-1 can elicit the production of pathogenic anti-dsDNA antibodies that can deposit in the kidney. Future studies are addressing the mechanism by which EBNA-1 can elicit these anti-dsDNA antibodies.
Ph.D., 1985, Columbia University
M. Phil., 1982
B.S., 1978, SUNY at Albany
How anti-DNA antibodies arise in Lupus.
What leads to a breakdown in the regulation of cells producing antibodies in Lupus.
Spatz, L., V. Saenko, A. Iliev, L. Jones, L. Geskin, and B. Diamond. 1997. Light chain usage in anti-dsDNA B cell subsets: Role in cell fate determination. J. Exp. Med 185: 1317-1326.
Bynoe, M.S., L. Spatz, and B. Diamond. 1999. Characterization of anti-DNA B cells that escape negative selection. Euro. J. Immunol. 29: 1304-1313.
Chu, Y.-P., D. Taylor, H-G., Yan, B. Diamond, and L. Spatz. 2002. Persistence of partially functional dsDNA binding B cells in mice transgenic for the heavy chain of an IgM anti-dsDNA antibody. Internat. Immunol. 14: 45-54.
Sundar, K., P. Gottlieb, S. Jacques, R. Villars, M-E. Benito, D. Taylor and L. Spatz. 2004. Expression of the Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1) in the mouse can elicit the production of anti-dsDNA antibodies. J. Autoimmunity. 23; 127-140.
Taylor, D.K., Ito, E., Thorn, M., Sundar, K., Tedder, T., and Spatz, L. 2006. Loss of tolerance of anti-dsDNA B cells in mice overexpressing CD19. Mol. Immunol. 11; 1776-1790.
Thorn, M., Lewis, R., Kantrowitz, S., Mumbey-Wafula, A., and Spatz, L. 2010. BAFF overexpression promotes anti-dsDNA B cell maturation and antibody secretion. Cellular Immunol. 261; 9-22.
Yadav, P., Tran, H., Ebegbe, R., Gottlieb P., Wei, H., Mumbey-Wafula, A., Kaplan, A. Kholdarova, E., and Spatz, L. in revision. EBNA-1 protein can elicit antibodies that cross-react with dsDNA. PLos One.
Spatz, L. Tolerance and Autoimmunity. In, Immunology, A Short Course, 6th Edition. 2009. R. Coico and G. Sunshine editors. John Wiley and Sons Inc., New York, NY