title: Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcγRIIB-deficient C57BL/6 mice.
abstract: We previously established an IgG Fc receptor IIB (FcγRIIB)-deficient C57BL/6 (B6)-congenic mouse strain (KO1), which spontaneously develops rheumatoid arthritis (RA), but not systemic lupus erythematosus (SLE). Here, we show that when Y chromosome-linked autoimmune acceleration (Yaa) mutation was introduced in KO1 strain (KO1.Yaa), the majority of KO1.Yaa mice did not develop RA, but instead did develop SLE. This phenotype conversion did not depend on autoantibody specificity, since KO1.Yaa mice, compared with KO1, showed a marked increase in serum levels of both lupus-related and RA-related autoantibodies. The increase in frequencies of CD69(+) activated B cells and T cells, and the spontaneous splenic GC formation with T follicular helper cell generation were manifest early in life of KO1.Yaa, but not KO1 and B6.Yaa, mice. Activated CD4(+) T cells from KO1.Yaa mice showed upregulated production of IL-21 and IL-10, compared with the finding in KO1 mice, indicating the possibility that this aberrant cytokine milieu relates to the disease phenotype conversion. Thus, our model is useful to clarify the shared and the disease-specific mechanisms underlying the clinically distinct systemic autoimmune diseases RA and SLE.
authors.affiliation: Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kawano
authors.forename: Qingshun
authors.initials: Q
authors.lastname: Lin
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Amano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaneko
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tsurui
authors.forename: Norihiro
authors.initials: N
authors.lastname: Tada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Shirai
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly; D014998:Y Chromosome
chemical_list: D001323:Autoantibodies; D016207:Cytokines; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG