Restricted specificity of peripheral alloreactive memory B cells in HLA-sensitized patients awaiting a kidney transplant

Kidney Int. 2015 Jun;87(6):1230-40. doi: 10.1038/ki.2014.390. Epub 2015 Jan 7.


The contribution of memory B cells in alloreactive humoral responses remains poorly understood. Here we tested the presence of circulating alloreactive memory B cells in 69 patients with end-stage renal disease under renal replacement therapy, using an in vitro memory B cell-stimulation assay combined with identification of IgG human leukocyte antigen (HLA) antibodies in culture supernatant. HLA antibody-producing memory B cells were evidenced only in patients carrying serum HLA antibodies following multiple classical HLA-immunizing events. In patients with a previous renal allograft, alloreactive memory B cells could be detected ranging from 6 to 32 years (mean 13.2 years) after transplantation. HLA antibodies produced by memory B cells were also detected in the corresponding sera and showed a restricted reactivity, targeting only a few epitopes shared by several HLA antigens. In contrast, serum HLA antibodies, not associated with the detection of specific memory B cells, showed a broader pattern of specificities. Thus, expansion and survival of alloreactive memory B cells is alloantigen driven, and their frequency is related to the 'strength' of HLA immunization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Fluorescent Antibody Technique
  • HLA Antigens / immunology*
  • Humans
  • Immunity, Humoral
  • Immunoglobulin G / analysis
  • Immunoglobulin G / blood*
  • Immunologic Memory*
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Time Factors


  • HLA Antigens
  • Immunoglobulin G