Selective recognition and elimination of nicotinic acetylcholine receptor-reactive B cells by a recombinant fusion protein AChR-Fc in myasthenia gravis in vitro.
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.
Chang
Ting
T
Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
Lin
Hong
H
Gao
Jie
J
Li
Wei
W
Xu
Jiang
J
Sun
Chen Jing
CJ
Li
Hang
H
Li
Fan Fan
FF
Song
Yue
Y
Ye
Jing
J
Li
Zhu Yi
ZY
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D006825:Hybridomas; D008212:Lymphocyte Depletion / Q000379:methods; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D017452:Receptors, IgG / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
C499173:FCGR2B protein, human; D017452:Receptors, IgG; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins