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

Abstract : 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.
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Submitted on : Friday, November 22, 2019 - 3:29:38 PM
Last modification on : Wednesday, October 27, 2021 - 4:04:03 PM

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Renaud Snanoudj, Frans H.J. Claas, Sebastiaan Heidt, Christophe Legendre, Lucienne Chatenoud, et al.. Restricted specificity of peripheral alloreactive memory B cells in HLA-sensitized patients awaiting a kidney transplant. Kidney International, Nature Publishing Group, 2015, 87 (6), pp.1230-1240. ⟨10.1038/ki.2014.390⟩. ⟨hal-02376379⟩

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