Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Y aa mutation into F c[gamma] RIIB -deficient C 57 BL /6 mice

• Published in: European journal of immunology 2013-03, Vol.43 (3), p.770-778
• Main Authors: Kawano, Shinya, Lin, Qingshun, Amano, Hirofumi, Kaneko, Toshiyuki, Nishikawa, Keiko, Tsurui, Hiromichi, Tada, Norihiro, Nishimura, Hiroyuki, Takai, Toshiyuki, Shirai, Toshikazu, Takasaki, Yoshinari, Hirose, Sachiko
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201243057

We previously established an I g G F c receptor IIB ( F c[gamma] RIIB )-deficient C 57 BL /6 ( B 6)-congenic mouse strain ( KO 1), which spontaneously develops rheumatoid arthritis ( RA ), but not systemic lupus erythematosus ( SLE ). Here, we show that when Y chromosome-linked autoimmune acceleration ( Y aa) mutation was introduced in KO 1 strain ( KO 1. Y aa), the majority of KO 1. Y aa mice did not develop RA , but instead did develop SLE . This phenotype conversion did not depend on autoantibody specificity, since KO 1. Y aa mice, compared with KO 1, showed a marked increase in serum levels of both lupus-related and RA -related autoantibodies. The increase in frequencies of CD 69 super(+) activated B cells and T cells, and the spontaneous splenic GC formation with T follicular helper cell generation were manifest early in life of KO 1. Y aa, but not KO 1 and B 6. Y aa, mice. Activated CD 4 super(+) T cells from KO 1. Y aa mice showed upregulated production of IL -21 and IL -10, compared with the finding in KO 1 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 .