Tolerance induction via B-cell delivered gene therapy

A master control of both the innate and adaptive immune system is the body's ability to distinguish between self and foreign entities. This is accomplished by the elimination of autoreactive leukocytes through a series of checkpoints both in the thymus (central deletion) and in the circulating periphery (peripheral tolerance), thus establishing tolerance to self-antigens. When one or more of these controls is disrupted, there is the potential for the development of autoimmune disease. Current available therapies for these diseases often rely on global immune suppression or expensive treatments that are not affordable to all. Herein, we describe a novel therapeutic technique in which tolerance to self can be re-established via B-cell delivered antigen-specific tolerogenic gene constructs. Furthermore, this technique shows promise in the gene therapeutic treatment of monogenic disorders and the acceptance of tissue transplants.