Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD.

Autor:	Poe JC; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Fang J; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA., Zhang D; Duke Cancer Institute, Durham, North Carolina, USA., Lee MR; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA., DiCioccio RA; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Su H; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Qin X; Duke Cancer Institute, Durham, North Carolina, USA., Zhang JY; Department of Dermatology, Duke University Medical Center, Durham, North Carolina, USA., Visentin J; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and.; Department of Immunology and Immunogenetics, Bordeaux University Hospital, Bordeaux, France.; UMR CNRS 5164 ImmunoConcEpT, Bordeaux University, Bordeaux, France., Bracken SJ; Department of Medicine, Division of Rheumatology and Immunology, Duke University Medical Center, Durham, North Carolina, USA., Ho VT; Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Wang KS; Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Rose JJ; Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA., Pavletic SZ; Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA., Hakim FT; Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA., Jia W; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Suthers AN; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Curry-Chisolm IM; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Horwitz ME; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and.; Duke Cancer Institute, Durham, North Carolina, USA., Rizzieri DA; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and.; Duke Cancer Institute, Durham, North Carolina, USA., McManigle WC; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and., Chao NJ; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and.; Duke Cancer Institute, Durham, North Carolina, USA.; Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA., Cardones AR; Department of Dermatology, Duke University Medical Center, Durham, North Carolina, USA., Xie J; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.; Duke Cancer Institute, Durham, North Carolina, USA., Owzar K; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.; Duke Cancer Institute, Durham, North Carolina, USA., Sarantopoulos S; Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, and.; Duke Cancer Institute, Durham, North Carolina, USA.; Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2023 Jun 08; Vol. 8 (11). Date of Electronic Publication: 2023 Jun 08.
DOI:	10.1172/jci.insight.169732
Abstrakt:	Alloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell-associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells continually develop under selective pressure from host alloantigens, aberrant B cell receptor (BCR) activation and IgG production can emerge and contribute to cGVHD pathobiology. To better understand molecular programing of B cells in allo-HCT, we performed scRNA-Seq analysis on high numbers of purified B cells from patients. An unsupervised analysis revealed 10 clusters, distinguishable by signature genes for maturation, activation, and memory. Within the memory B cell compartment, we found striking transcriptional differences in allo-HCT patients compared with healthy or infected individuals, including potentially pathogenic atypical B cells (ABCs) that were expanded in active cGVHD. To identify intrinsic alterations in potentially pathological B cells, we interrogated all clusters for differentially expressed genes (DEGs) in active cGVHD versus patients who never had signs of immune tolerance loss (no cGVHD). Active cGVHD DEGs occurred in both naive and BCR-activated B cell clusters. Remarkably, some DEGs occurred across most clusters, suggesting common molecular programs that may promote B cell plasticity. Our study of human allo-HCT and cGVHD provides understanding of altered B cell memory during chronic alloantigen stimulation.
Databáze:	MEDLINE
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