Specific depletion of autoreactive B lymphocytes by a recombinant fusion protein in vitro and in vivo.

Antigen-specific B cells are key players in many autoimmune diseases through the production of autoreactive antibodies that can cause severe tissue damage and malfunction. We have designed and expressed a fusion protein, referred to as MOG-Fc, composed of the extracellular Ig-like domain of human myelin oligodendrocyte glycoprotein (MOG) and the C(H)2 and C(H)3 domains of the human IgG1 heavy chain. The dimerized fusion protein was capable of mediating cytotoxicity against a MOG-reactive hybridoma line in vitro. Likewise, MOG-Fc significantly reduced the number of circulating MOG-reactive B cells in an anti-MOG Ig heavy chain knock-in mouse model. Our study shows that autoantigen-reactive B lymphocytes can be efficiently and selectively eliminated by an autoantigen Fcgamma1 fusion protein in vitro as well as in vivo. Such fusion proteins may provide a platform for the development of highly selective therapeutic approaches.