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.
Zocher
Marcel
M
Micromet AG, 81477 Munich, Germany.
Baeuerle
Patrick A
PA
Dreier
Torsten
T
Iglesias
Antonio
A
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D001324:Autoantigens / Q000235:genetics*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007074:Immunoglobulin G; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011993:Recombinant Fusion Proteins