Blimp-1 siRNA inhibits B cell differentiation and prevents the development of lupus in mice

Abstract

Cumulative evidence suggest that B-lymphocytes play a role in the development of systemic lupus erythematosus (SLE). Thus, the therapeutic approach targeting specific B cells provides a promising way to treat SLE. Blimp-1 (B lymphocyte induced maturation protein), a transcriptional factor, controls the terminal differentiation of mature B cells to plasma cells. To explore the potential of Blimp-1 in the SLE development, we constructed the adenovirus encoding Blimp-1 siRNA, and injected it into BWF1 lupus mice. The results demonstrated that Blimp-1 siRNA decreased the Blimp-1 expression of B cells by regulating XBP-1 (X Box binding protein-1), BCMA (B-cell maturation antigen) expression through c-myc pathway. In addition, Blimp-1 siRNA eliminated anti-dsDNA antibody-producing plsma cells, reduced serum anti-dsDNA antibody levels and impeded the development of lupus. Therefore, our data provide the insight into the mechanism of Blimp-1 in SLE development and might represent a promising therapeutic strategy for autoantibody-mediated diseases.