Abstract
Ab maturation as well as memory B and plasma cell differentiation occur primarily in the germinal centers (GCs). Systemic lupus erythematosus (SLE) may develop as a result of enhanced GC activity. Previous studies have shown that the dysregulated STAT3 pathway is linked to lupus pathogenesis. However, the exact role of STAT3 in regulating SLE disease progression has not been fully understood. In this study, we demonstrated that STAT3 signaling in B cells is essential for GC formation and maintenance as well as Ab response. Increased cell apoptosis and downregulated Bcl-xL and Mcl-1 antiapoptotic gene expression were found in STAT3-deficient GC B cells. The follicular helper T cell response positively correlated with GC B cells and was significantly decreased in immunized B cell STAT3-deficient mice. STAT3 deficiency also led to the defect of plasma cell differentiation. Furthermore, STAT3 deficiency in autoreactive B cells resulted in decreased autoantibody production. Results obtained from B cell STAT3-deficient B6.MRL/lpr mice suggest that STAT3 signaling significantly contributes to SLE pathogenesis by regulation of GC reactivity, autoantibody production, and kidney pathology. Our findings provide new insights into the role of STAT3 signaling in the maintenance of GC formation and GC B cell differentiation and identify STAT3 as a novel target for treatment of SLE.