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

Renaud Snanoudj (1) , Frans H.J. Claas , Sebastiaan Heidt , Christophe Legendre (2) , Lucienne Chatenoud (3) , Sophie Candon (4)

1 Hôpital Foch [Suresnes]
2 Service de néphrologie adultes [CHU Necker]
3 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
4 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices

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.

Mots clés: Continuous renal replacement therapy; Lymphocytes

Domaines: Immunité adaptative; Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Urologie et Néphrologie

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, 2015, 87 (6), pp.1230-1240. ⟨10.1038/ki.2014.390⟩. ⟨hal-02376379⟩