Up-regulation of transcription factor Blimp1 in systemic lupus erythematosus

Mol Immunol. 2013 Dec;56(4):574-82. doi: 10.1016/j.molimm.2013.05.241. Epub 2013 Aug 1.

Abstract

Purpose: B lymphocyte induced maturation protein 1 (Blimp1) is a transcription factor that is critical for differentiation and antibody production in plasma cells. In order to understand the mechanism of systemic lupus erythematosus (SLE), the role of Blimp1 expression was studied in patients with SLE and in healthy control subjects. And Blimp1 tissue distribution in MRL/lpr lupus mice was also investigated.

Methods: The mRNA expression level of Blimp1 was analyzed by fluorescent real time PCR and compared between the 40 SLE patients and 30 control subjects. Expression of CD138, CD27 and CD19 in peripheral blood cells was analyzed by flow cytometry. Blimp1 mRNA and protein expression levels and tissue distribution in the kidneys, spleen and lymph nodes of MRL/lpr lupus and normal mice were analyzed.

Results: Blimp1 mRNA expression level was 2.1 times greater in the SLE group as compared to the control group. The increased mRNA expression of Blimp1 seemed to be related to SLE disease activity and anti-nuclear antibody (ANA) titer. In SLE patients, the CD138+ plasma cells increased as the CD27+ cells decreased. Compared with normal mice, Blimp1 was strongly expressed in the kidneys, lymph nodes and spleen of MRL/lpr lupus mice. The expression level of Blimp1 mRNA in the kidneys, lymph nodes and spleen of MRL/lpr lupus mice was much higher than normal mice (1.76, 2.02, and 2.05 times greater, respectively, P<0.05). Similarly, protein levels in the above mentioned organs were also much higher (1.54, 1.99, and 2.21 times greater, respectively, P<0.05).

Conclusions: The elevated expression of Blimp1 in SLE patients and in the lupus mouse model is correlated with increases in plasma cells, autoantibodies and disease activity. It is closely related to differentiation of B-lymphocytes, antibody production and renal lesions. Blimp1 may play a role in SLE disease development.

Keywords: B lymphocyte induced maturation protein1; Plasma cells; Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Antinuclear / blood
  • Antigens, CD19 / blood
  • B-Lymphocytes / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Kidney / metabolism
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / pathology
  • Lymph Nodes / metabolism
  • Male
  • Mice
  • Mice, Inbred MRL lpr
  • Middle Aged
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / metabolism
  • Syndecan-1 / blood
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood
  • Up-Regulation*
  • Young Adult

Substances

  • Antibodies, Antinuclear
  • Antigens, CD19
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Syndecan-1
  • Transcription Factors
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1