Transgenic mouse models for B-cell dominant autoimmune diseases

To study the molecular mechanism for the development of B-cell dominant autoimmune diseases, several autoantibody transgenic mouse models were established. These studies have revealed that the escape of autoreactive B cells from clonal deletion or functional inactivation (clonal anergy) alone is not enough to develop autoimmune disease. Indeed, additional factors such as infections, cytokines and the costimulatory help of T cells are required for the activation of autoreactive B cells. The requirement for activation of autoreactive clones is also shown for the development of T-cell dominant autoimmune diseases in a T-cell receptor transgenic model. These findings will clarify the two-step mechanism of autoimmune disease: appearance and activation of autoreactive lymphocytes.