LDV02 SPECIFIC ELIMINATION OF ANTI-HLA ANTIBODY-PRODUCING B CELLS IN AN IN VIVO MOUSE MODEL BY USING CHIMERIC HLA ANTIBODY RECEPTOR (CHAR) T CELLS Importantly, AM B cells were detected within kidney allografts along with their restricted IGHV sequences.Ĭonclusions: This study delineates a pivotal role for AM B cells in promoting humoral responses and ABMR in organ transplantation, and identifies the IL-21/T-bet axis as an important therapeutic target. AM cells preferentially accumulated in blood of patients with severe ABMR manifestations including late-onset of rejection post-transplant, presence of IgG3 DSAs, and increased vascular inflammation in kidney allografts. IL-21 was a potent inducer of AM cells, their upregulation of T-bet and IL-21R, and promoted their differentiation into DSA-producing plasma cells. AM cells in patients undergoing ABMR markedly upregulated IL-21R, and the downstream transcription factors, IRF4 and Blimp1, displayed a plasma cell precursor transcriptional profile and expressed more restricted IGHV sequences, reflective of clonal expansion, when compared to other memory B-cell subsets ( p < 0.001). AM cells were less frequent in DSA+ABMR patients and at baseline levels in DSA patients ( p < 0.001). Results: We identified expanded numbers of CD27 +CD21 - activated memory (AM) B cells that expressed the transcription factor T-bet in blood of patients who developed DSAs and progressed to ABMR. There were 48 patients without DSAs of those with DSAs, ABMR emerged in 20 patients, but not in 28 patients. ![]() Methods: In a cohort of 96 kidney transplant recipients, we performed 22-color spectral flow cytometry, RNA-seq and in vitro assays to profile circulating B cells, as well as multiplex immunofluorescence and RNA-seq to profile infiltrating B cells in allograft biopsies. ![]() Yet, the cellular states underlying alloreactive B-cell responses and the molecular components controlling them remain unclear. ![]() Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USAīackground: Donor-specific antibodies (DSAs) and ensuing development of antibody-mediated rejection (ABMR) are detrimental to organ transplants. Kevin Louis 1, Elodie Bailly 2,3, Camila Macedo 3, Bala Ramaswami 3, Parmjeet Randhawa 3, Geetha Chalasani 3, Adriana Zeevi 3, Carmen Lefaucheur 2, Diana Metes 3ġParis Translational Center for Organ Transplantation, Paris, France 2Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale U970, Université de Paris, Paris, France 3Department of Surgery, Thomas E. ESOT LEONARDO DA VINCI TRANSPLANT RESEARCH INNOVATION AWARD LDV01 IL-21 DRIVEN EXPANSION AND REPROGRAMMING OF T-BET EXPRESSING B CELLS DURING ANTIBODY-MEDIATED REJECTION OF KIDNEY TRANSPLANTS
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