title: Human proximal tubule epithelial cells modulate autologous B-cell function.
abstract: BACKGROUND
  Descriptions of inflammatory cells infiltrating the human kidney rarely mention B cells, other than in the specific scenario of transplantation. In these reports, B cells are localized almost exclusively within the kidney tubulointerstitium where they are ideally placed to interact with proximal tubule epithelial cells (PTEC). We have previously shown that activated PTEC down-modulate autologous T lymphocyte and dendritic cell function. In this report, we extend these prior studies to describe PTEC-B cell interactions.
  
  
  METHODS
  Stimulated B cells were cultured in the absence or presence of activated autologous human PTEC and monitored for proliferation, surface antigen expression, cytokine secretion and antibody (Ab) production.
  
  
  RESULTS
  PTEC decreased B cell proliferative responses, whilst B cells cultured in the presence of PTEC displayed decreased levels of CD27, a marker of plasma B cells and memory cells. Interestingly, autologous PTEC also significantly decreased the number of B cells secreting both IgG and IgM and overall levels of Ab production. Transwell studies demonstrated that this modulation was primarily contact-dependent, and blocking studies with anti-PD-L1 led to partial restoration in Ab production. Further blocking studies targeting soluble HLA-G (sHLA-G) and IDO, two other immunoinhibitory molecules also up-regulated in our activated PTEC, demonstrated minor restoration of Ab responses.
  
  
  CONCLUSIONS
  We report, for the first time, that PTEC are also able to modulate autologous B-cell phenotype and function via complex contact-dependent (PD-L1), soluble (sHLA-G) and intracellular (IDO) factors. We hypothesize that such mechanisms may have evolved to maintain peripheral immune-homeostasis, especially within the inflammatory milieu that exists within many kidney diseases.
authors.affiliation: Conjoint Renal Laboratory, Pathology Queensland, Brisbane, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sampangi
authors.affiliation: Conjoint Renal Laboratory, Pathology Queensland, Brisbane, Australia.
authors.forename: Xiangju
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Travis
authors.initials: T
authors.lastname: Klein
authors.affiliation: Conjoint Renal Laboratory, Pathology Queensland, Brisbane, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Sadia
authors.initials: S
authors.lastname: Afrin
authors.affiliation: Conjoint Renal Laboratory, Pathology Queensland, Brisbane, Australia Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Healy
authors.affiliation: Conjoint Renal Laboratory, Pathology Queensland, Brisbane, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia Medical School, University of Queensland, Brisbane, Australia.
authors.forename: Ray
authors.initials: R
authors.lastname: Wilkinson
authors.affiliation: Conjoint Renal Laboratory, Pathology Queensland, Brisbane, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Kassianos
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D060890:B7-H1 Antigen / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000502:physiology*; D059951:HLA-G Antigens / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D009395:Nephritis, Interstitial / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D059951:HLA-G Antigens
keywords: B cells; immune modulation; kidney; proximal tubule epithelial cells