title: Is there B cell involvement in a rat model of spontaneous idiopathic nephrotic syndrome treated with LF15-0195?
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: INSERM U1064, 44093, Nantes, France, Ludmilla.Leberre@univ-nantes.fr.
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Le Berre
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Tilly
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D013997:Time Factors
chemical_list: D006146:Guanidines; C434185:LF 150195; D012333:RNA, Messenger; D008942:Mitoxantrone