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Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into Fc?RIIB-deficient C57BL/6 mice

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Published:25th Mar 2020
We previously established an IgG Fc receptor IIB (Fc?RIIB)-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 spontaneously splenic GC formation with T follicular helper (TFH) 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 up-regulated 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.

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