title: Prednisone treatment inhibits the differentiation of B lymphocytes into plasma cells in MRL/MpSlac-lpr mice.
abstract: OBJECTIVE
  A number of evidence shows that the differentiation of B lymphocytes into plasma cells plays an important role in lupus pathogenesis. In this study we investigated how prednisone, a classical therapeutic drug for autoimmune diseases, regulated plasma cell differentiation in MRL/MpSlac-lpr mice.
  
  
  METHODS
  MRL/lpr mice were treated with prednisone (2.5 or 5 mg·kg(-1)·d(-1), ig) for 13 weeks, and the proteinuria levels and survival times were monitored. After the mice were euthanized, blood sample, spleen and thymus were collected. The serum levels of anti-dsDNA antibody, anti-nuclear antibody, IL-21, and IL-10 were detected using ELISA kits. Subsets of splenic B and T lymphocytes were quantified with flow cytometry. Transcription factor Blimp-1 and Bcl-6 expression was determined using qPCR and Western blot.
  
  
  RESULTS
  Prednisone treatment dose-dependently attenuated the lupus symptoms in MRL/lpr mice with decreased proteinuria levels, prolonged survival times, decreased serum anti-nuclear antibody levels, and reduced spleen and thymus indices. Prednisone treatment also significantly decreased the elevated percentages of plasma cells and plasma cell precursors, decreased the percentages of activated T cells, and increased the frequency of CD4(+)CD62L(+) cells, demonstrated that decreased anti-nuclear antibodies and improvements in lupus symptoms were associated with decreased plasma cells. Furthermore, prednisone treatment decreased serum IL-21 and IL-10 levels and reduced the expression of splenic Blimp-1 and Bcl-6 (two key regulatory factors for plasma cell differentiation) in MRL/lpr mice.
  
  
  CONCLUSIONS
  Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/lpr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
authors.forename: Shang-xue
authors.initials: SX
authors.lastname: Yan
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Deng
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
authors.forename: Qing-tong
authors.initials: QT
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019463:Mice, Inbred MRL lpr; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use*; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D016207:Cytokines; D011241:Prednisone