Human proximal tubule epithelial cells modulate autologous B-cell function

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2015-10, Vol.30 (10), p.1674-1683
• Main Authors: Sampangi, Sandeep, Wang, Xiangju, Beagley, Kenneth W, Klein, Travis, Afrin, Sadia, Healy, Helen, Wilkinson, Ray, Kassianos, Andrew J
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - physiology; B7-H1 Antigen - metabolism; Cell Communication - physiology; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - physiology; HLA-G Antigens - metabolism; Humans; Kidney Tubules, Proximal - physiology; Nephritis, Interstitial - immunology; Nephritis, Interstitial - metabolism; T-Lymphocytes - immunology
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfv242

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. 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. 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. 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.