Selective recognition and elimination of nicotinic acetylcholine receptor-reactive B cells by a recombinant fusion protein AChR-Fc in myasthenia gravis in vitro

Abstract

AChR-reactive B cells play a key role in the pathogenesis of myasthenia gravis (MG) by producing autoantibodies. Selective elimination of AChR-reactive B cells will be a promising way to treat MG. Thus, we generated a fusion protein (referred to as AChR-Fc) composed of the human extracellular domain of AChR α1 subunit and the Fc domain of the human IgG1 heavy chain, which could bind both to AChR-reactive BCR and FcγRIIB on the surface of AChR-reactive B cells. Our results showed that AChR-Fc inhibited the proliferation of AChR-specific hybridoma cells, promoted their apoptosis, and mediated cytotoxicity by cross-linking effector cells and complement. Likewise, AChR-Fc significantly reduced the number of AChR-reactive B cells from spleen of Lewis rats immunized with AChR ex vivo.