Intrarenal B Cell Cytokines Promote Transplant Fibrosis and Tubular Atrophy

G. H. Tse, C. J. C. Johnston, D. Kluth, M. Gray, D. Gray, J. Hughes, L. P. Marson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Renal transplantation is the optimum treatment for end‐stage renal failure. B cells have been identified in chronic allograft damage (CAD) and associated with the development of tertiary lymphoid tissue within the human renal allograft. We performed renal transplantation in mice to model CAD and identified B cells forming tertiary lymphoid tissue with germinal centers. Intra‐allograft B220+ B cells comprised of IgMhigh CD23 B cells, IgMlo CD23+ B cells, and IgMlo CD23 B cells with elevated expression of CD86. Depletion of B cells with anti‐CD20 was associated with an improvement in CAD but only when administered after transplantation and not before. Isolated intra‐allograft B cells were cultured and shown to synthesize multiple cytokines, the most abundant of these were GRO‐α (CXCL1), RANTES (CCL5), IL‐6 and MCP‐1 (CCL2). Tubular loss was observed with T cell accumulation within the allograft and development of interstitial fibrosis, whilst type III collagen deposition was observed in areas of F4/80+ macrophages and PDGFR‐β+ and transgelin+ fibroblasts, all of which were reduced by B cell depletion. We have shown that intra‐allograft B cells are key mediators of CAD. B cells possibly contribute to CAD by intra‐allograft secretion of cytokines and chemokines.
Original languageEnglish
Pages (from-to)3067-3080
JournalAmerican Journal of Transplantation
Issue number12
Early online date24 Jul 2015
Publication statusPublished - Dec 2015

Keywords / Materials (for Non-textual outputs)

  • B cells
  • Chronic allograft damage
  • Mouse model
  • Renal Transplant


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