title: 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.
authors.affiliation: 1] Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Hôpital Necker, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cite, Paris, France [3] Service de Transplantation Rénale Adulte, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Snanoudj
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Heidt
authors.affiliation: 1] Université Paris Descartes, Sorbonne Paris Cite, Paris, France [2] Service de Transplantation Rénale Adulte, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: 1] Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Hôpital Necker, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
authors.affiliation: 1] Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Hôpital Necker, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood*; D007156:Immunologic Memory; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G