Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus.
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.
Lin
Qingshun
Q
Department of Pathology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Hou
Rong
R
Sato
Aya
A
Ohtsuji
Mareki
M
Ohtsuji
Naomi
N
Nishikawa
Keiko
K
Tsurui
Hiromichi
H
Amano
Hirofumi
H
Amano
Eri
E
Sudo
Katsuko
K
Nishimura
Hiroyuki
H
Shirai
Toshikazu
T
Hirose
Sachiko
S
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*
C499172:Fcgr2b protein, mouse; D011961:Receptors, Fc; D017452:Receptors, IgG