Presence of intragraft B cells during acute renal allograft rejection is accompanied by changes in peripheral blood B cell subsets

Clin Exp Immunol. 2019 Jun;196(3):403-414. doi: 10.1111/cei.13269. Epub 2019 Feb 17.

Abstract

B cells have various functions, besides being plasma cell precursors. We determined the presence of intragraft B cells at time of acute rejection (AR) and looked for correlates of B cell involvement in peripheral blood. Renal biopsies at time of AR or stable graft function were analysed for the presence of B cells and B cell-related gene expression, as well as C4d staining. Peripheral blood B cell subset distribution was analysed at various time-points in patients with AR and controls, alongside serum human leucocyte antigen (HLA) antibodies. AR was accompanied by intragraft CD20+ B cells, as well as elevated CD20 (MS4A1) and CD19 gene expression compared to controls. B cell infiltrates were proportional to T cells, and accompanied by the chemokine pair C-X-C motif chemokine ligand 13 (CXCL13)-C-X-C motif chemokine receptor 5 (CXCR5) and B cell activating factor (BAFF). Peripheral blood memory B cells were decreased and naive B cells increased at AR, in contrast to controls. While 22% of patients with AR and 5% of controls showed de-novo donor-specific antibodies (DSA), all biopsies were C4d-negative. These results suggest a role for B cells in AR by infiltrating the graft alongside T cells. We hypothesize that the shift in peripheral blood B cell composition is related to the graft infiltration at time of AR.

Keywords: B cell infiltration; T cell/B cell interaction; flow cytometry; memory B cell.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Antigens, CD20 / metabolism
  • B-Lymphocytes / immunology*
  • Blood Circulation
  • Cell Movement
  • Chemokine CXCL13 / metabolism
  • Female
  • Graft Rejection / immunology*
  • Graft Survival / immunology*
  • Humans
  • Immunologic Memory
  • Isoantibodies / blood
  • Kidney / pathology*
  • Kidney Transplantation*
  • Lymphocyte Subsets / immunology*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antigens, CD20
  • Chemokine CXCL13
  • Isoantibodies