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

Hum Immunol. 2013 Mar;74(3):297-301. doi: 10.1016/j.humimm.2012.11.019. Epub 2012 Dec 7.

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.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • Antibodies, Antinuclear / metabolism
  • B-Cell Maturation Antigen / immunology
  • B-Cell Maturation Antigen / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Female
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • Mice
  • Mice, Inbred NZB
  • Mice, Inbred Strains
  • Plasma Cells / cytology
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-myc / immunology
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference / immunology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / immunology
  • Regulatory Factor X Transcription Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1

Substances

  • Antibodies, Antinuclear
  • B-Cell Maturation Antigen
  • DNA-Binding Proteins
  • Myc protein, mouse
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Regulatory Factor X Transcription Factors
  • Tnfrsf17 protein, mouse
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • Positive Regulatory Domain I-Binding Factor 1