Project 170482

The immune system plays an important role in discriminating between proteins that are foreign to the body, such as those in the bacteria and viruses that cause infections, and proteins that are normal parts of the body, such as those found in organs like the kidney and the brain. Foreign proteins are attacked preventing overwhelming infection while self-proteins are normally left unharmed. We believe that Systemic Lupus Erythematosus (SLE) results from defects in the immune system that lead to abnormal activation of cells that react to self-proteins. In the immune system two classes of cells, T and B cells, act in concert to mount an immune response. In many strains of mice that develop a lupus-like illness, B cell functional abnormalities play a central role in the pathogenesis of disease, yet the function of B cells in human lupus has not been well explored. Nevertheless, we, and others have shown that the B cells of humans with lupus are abnormally activated suggesting that they too have altered function. Here we seek to identify the functional abnormalities in the B cells of lupus patients and to determine whether they lead to altered responses to self-proteins. Identification of such abnormalities could ultimately lead to characterization of the underlying biochemical and genetic defects that produce SLE and more effective therapies for this condition.