title: Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus.
abstract: The autoimmune-type Fcgr2b with deletion polymorphism in AP-4-binding site in the promoter region is suggested to be one most plausible susceptibility gene for systemic lupus erythematosus (SLE). We previously found that there is a strong epistatic interaction between the autoimmune-type Fcgr2b polymorphism and Y chromosome-linked autoimmune acceleration (Yaa) mutation, thus severe SLE observed in BXSB males neither develops in BXSB females nor in the congenic BXSB.IIB(B6) males carrying wild C57BL/6-type Fcgr2b. Present studies examined whether the wild-type Fcgr2b could suppress SLE in mice carrying Yaa-unrelated SLE susceptibility genes. Comparison of disease features between SLE-prone (NZW x BXSB) F1 females and the congenic (NZW x BXSB.IIB(B6)) F1 females carrying wild-type Fcgr2b showed that, as compared with findings in the former, SLE features including activation/proliferation of not only B cells but also T cells and monocytes/macrophages were all inhibited in the latter. It was concluded that the autoimmune-type Fcgr2b promotes and the wild-type inhibits SLE through mechanisms that promote and suppress activation/proliferation of a wide variety of immune cells, respectively. Thus, the Fcgr2b polymorphism is a key genetic element for not only Yaa-related but also Yaa-unrelated lupus.
authors.affiliation: Department of Pathology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Qingshun
authors.initials: Q
authors.lastname: Lin
authors.forename: Rong
authors.initials: R
authors.lastname: Hou
authors.forename: Aya
authors.initials: A
authors.lastname: Sato
authors.forename: Mareki
authors.initials: M
authors.lastname: Ohtsuji
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohtsuji
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tsurui
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Amano
authors.forename: Eri
authors.initials: E
authors.lastname: Amano
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishimura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Shirai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D004843:Epistasis, Genetic / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D051379:Mice; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011961:Receptors, Fc / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: C499172:Fcgr2b protein, mouse; D011961:Receptors, Fc; D017452:Receptors, IgG