BACKGROUND: The Buffalo/Mna (Buff/Mna) rat spontaneously develops idiopathic nephrotic syndrome (INS), and its nephropathy recurs after the renal transplantation of a healthy graft. Only LF15-0195 is able to cause regression of the Buff/Mna nephropathy and to induce regulatory T cells, which decrease proteinuria when transferred into proteinuric Buff/Mna rats. Based on previous research on B cells in human INS, we evaluated the involvement of B cells in our model and the impact of LF15-0195. METHODS: We studied the effect of LF15-0195 on peripheral B cells by flow cytometry and quantitative reverse transcription-polymerase chain reaction. B cells were purified from LF15-0195-treated Buff/Mna rats in remission, and transferred into proteinuric Buff/Mna rats. We treated the Buff/Mna rats with mitoxantrone and measured the depletion of B/T cells in parallel with proteinuria. RESULTS: LF15-0195 changed the phenotype of B cells: the number of naïve mature B cells increased significantly, while the number of switched, transitional 1, and transitional 2 B cells decreased. There were no changes in the amount of memory, activated or regulatory B cells. We observed a significant increase of immunoglobulin (Ig)M mRNA transcripts in the LF15-0195-treated Buff/Mna B cells compared to controls, but no difference in the level of IgG. This profile is consistent with a block in B cell maturation at the IgM to IgG switch. The transfer of B cells from LF15-0195-treated rats into proteinuric Buff/Mna rats did not have an effect on proteinuria. Mitoxantrone, despite causing a significant depletion of B cells, did not reduce proteinuria. CONCLUSION: Despite LF15-0195 acting on B cells, the beneficial effects of this drug on nephrotic syndrome did not involve the induction of regulatory B cells. Moreover, the B cell depletion was not effective in reducing proteinuria, indicating that B cells are not a therapeutic target.
BACKGROUND: The Buffalo/Mna (Buff/Mna) rat spontaneously develops idiopathic nephrotic syndrome (INS), and its nephropathy recurs after the renal transplantation of a healthy graft. Only LF15-0195 is able to cause regression of the Buff/Mna nephropathy and to induce regulatory T cells, which decrease proteinuria when transferred into proteinuric Buff/Mna rats. Based on previous research on B cells in human INS, we evaluated the involvement of B cells in our model and the impact of LF15-0195. METHODS: We studied the effect of LF15-0195 on peripheral B cells by flow cytometry and quantitative reverse transcription-polymerase chain reaction. B cells were purified from LF15-0195-treated Buff/Mna rats in remission, and transferred into proteinuric Buff/Mna rats. We treated the Buff/Mna rats with mitoxantrone and measured the depletion of B/T cells in parallel with proteinuria. RESULTS: LF15-0195 changed the phenotype of B cells: the number of naïve mature B cells increased significantly, while the number of switched, transitional 1, and transitional 2 B cells decreased. There were no changes in the amount of memory, activated or regulatory B cells. We observed a significant increase of immunoglobulin (Ig)M mRNA transcripts in the LF15-0195-treated Buff/Mna B cells compared to controls, but no difference in the level of IgG. This profile is consistent with a block in B cell maturation at the IgM to IgG switch. The transfer of B cells from LF15-0195-treated rats into proteinuric Buff/Mna rats did not have an effect on proteinuria. Mitoxantrone, despite causing a significant depletion of B cells, did not reduce proteinuria. CONCLUSION: Despite LF15-0195 acting on B cells, the beneficial effects of this drug on nephrotic syndrome did not involve the induction of regulatory B cells. Moreover, the B cell depletion was not effective in reducing proteinuria, indicating that B cells are not a therapeutic target.
Authors: Valérie Duplan; Patrick Dutartre; Lennart T Mars; Roland S Liblau; Philippe Druet; Abdelhadi Saoudi Journal: J Immunol Date: 2003-02-15 Impact factor: 5.422
Authors: Jinming Yang; Suzanne M Bernier; Thomas E Ichim; Mu Li; Xiaoping Xia; Dejun Zhou; Xuyan Huang; Gill H Strejan; David J White; Robert Zhong; Wei-Ping Min Journal: J Leukoc Biol Date: 2003-09 Impact factor: 4.962