Prednisone treatment inhibits the differentiation of B Iymphocytes into plasma cells in MRL/MpSlac-lpr mice  

作　　者：Shang-xue YAN Xiao-mei DENG Qing-tong WANG Xiao-jing SUN Wei WEI 

机构地区：[1]Institute of Clinical Pharmacology, Anhui Medical University [2] Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry ofEducation, Hefei 230032, China

出　　处：《Acta Pharmacologica Sinica》2015年第11期1367-1376,共10页中国药理学报（英文版）

基　　金：Acknowledgements This work was financially supported by the National Natural Science Foundation of China （No 81173075, 81330081, and 81202541） and the Natural Science Foundation of Anhui Prov- ince （No KJ2011A177）.

摘　　要：Aim： 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/Ipr 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/Ipr 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/Ipr mice. Conclusion： Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/Ipr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.Aim： 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/Ipr 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/Ipr 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/Ipr mice. Conclusion： Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/Ipr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.

关 键 词：upus erythematosus MRL/Ipr mice PREDNISONE plasma cell differentiation INTERLEUKIN-21 interleukin-10 BLIMP-1 Bcl-6 

分 类 号：Q813[生物学—生物工程] S858.28[农业科学—临床兽医学]