Our laboratory is interested in understanding  how autoreactive T and B cells are regulated in normal immune system and what  goes wrong in autoimmunity. We have been exploiting transgenic and  gene-targeting technology to engineer new mouse models for rheumatoid  arthritis. Major questions tackled are why tolerance fails in these models,  what triggers the autoimmune processes, how genetic background affects  tolerance, and differential signaling by B cell receptor in tolerance  induction. Most recently, we have been utilizing our mouse models to understand  the mechanisms of B cell-depletion therapy by rituximab, which is effective in  treating rheumatoid arthritis and other autoimmune diseases.