PMID- 25565312 OWN - NLM STAT- MEDLINE DCOM- 20160301 LR - 20150530 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 87 IP - 6 DP - 2015 Jun TI - Restricted specificity of peripheral alloreactive memory B cells in HLA-sensitized patients awaiting a kidney transplant. PG - 1230-40 LID - 10.1038/ki.2014.390 [doi] AB - 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. FAU - Snanoudj, Renaud AU - Snanoudj R AD - 1] Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Hopital Necker, Paris, France [2] Universite Paris Descartes, Sorbonne Paris Cite, Paris, France [3] Service de Transplantation Renale Adulte, Hopital Necker, Assistance Publique-Hopitaux de Paris, Paris, France. FAU - Claas, Frans H J AU - Claas FH AD - Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. FAU - Heidt, Sebastiaan AU - Heidt S AD - Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. FAU - Legendre, Christophe AU - Legendre C AD - 1] Universite Paris Descartes, Sorbonne Paris Cite, Paris, France [2] Service de Transplantation Renale Adulte, Hopital Necker, Assistance Publique-Hopitaux de Paris, Paris, France. FAU - Chatenoud, Lucienne AU - Chatenoud L AD - 1] Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Hopital Necker, Paris, France [2] Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. FAU - Candon, Sophie AU - Candon S AD - 1] Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Hopital Necker, Paris, France [2] Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150107 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (HLA Antigens) RN - 0 (Immunoglobulin G) SB - IM MH - Adult MH - B-Lymphocytes/*immunology MH - Cells, Cultured MH - Female MH - Fluorescent Antibody Technique MH - HLA Antigens/*immunology MH - Humans MH - Immunity, Humoral MH - Immunoglobulin G/analysis/*blood MH - *Immunologic Memory MH - Kidney Failure, Chronic/*immunology/surgery MH - *Kidney Transplantation MH - Male MH - Middle Aged MH - Time Factors EDAT- 2015/01/08 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/01/08 06:00 PHST- 2014/07/04 00:00 [received] PHST- 2014/10/01 00:00 [revised] PHST- 2014/10/09 00:00 [accepted] PHST- 2015/01/08 06:00 [entrez] PHST- 2015/01/08 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] AID - S0085-2538(15)30139-3 [pii] AID - 10.1038/ki.2014.390 [doi] PST - ppublish SO - Kidney Int. 2015 Jun;87(6):1230-40. doi: 10.1038/ki.2014.390. Epub 2015 Jan 7.