B-cell based gene therapy for autoimmune diseases.

The essence of the adaptive immune system is self tolerance, which is maintained by various central and peripheral check points. However, the tolerance mechanisms can be broken in autoimmune disease conditions due to genetic predisposition and environmental triggers. As a consequence, a patient's tissue is attacked by his/her own adaptive immune system. An ideal therapy for autoimmune diseases should include methods to re-establish tolerance to the underpinning autoantigen(s). During the last 15 years our lab has been dedicated to developing a novel B-cell gene therapy approach for antigen-specific tolerance induction. This approach has been successfully applied to at least five different animal models for human autoimmune diseases. In this article, we will discuss many of our successful preclinical studies using the B-cell gene therapy approach to induce tolerance, as well as similar studies from others. Particular focus will be given to the tolerance induction mechanisms that have been revealed from these studies.