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

• DOI: 10.1172/jci.insight.169732
• Publication Date: 2023-05-02T16:00:52Z
• Authors: Jonathan C. Poe; Jiyuan Fang; Dadong Zhang; Marissa R. Lee; Rachel A. DiCioccio; Hsuan Su; Xiaodi Qin; Jennifer Y. Zhang; Jonathan Visentin; Sonali J. Bracken; Vincent T. Ho; Kathy S. Wang; Jeremy J. Rose; Steven Z. Pavletic; Frances T. Hakim; Wei Jia; Amy N. Suthers; Itaevia M. Curry-...; Mitchell E. Horwitz; David A. Rizzieri; William C. McManigle; Nelson J. Chao; Adela R. Cardones; Jichun Xie; Kouros Owzar; Stefanie Sarantop...
• Keywords: Compartment (ship); Molecular cell biology

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 cells continually develop under selective pressure from host alloantigens, aberrant receptor (BCR) activation and IgG production emerge contribute to cGVHD pathobiology. To better understand molecular programing of in allo-HCT, we performed scRNA-Seq analysis on high numbers purified patients. An unsupervised revealed 10 clusters, distinguishable by signature genes for maturation, activation, memory. Within the memory compartment, found striking transcriptional differences allo-HCT patients compared with healthy or infected individuals, including potentially pathogenic atypical (ABCs) that were expanded active cGVHD. identify intrinsic alterations pathological cells, interrogated all clusters differentially expressed (DEGs) versus who never had signs immune tolerance loss (no cGVHD). Active DEGs occurred both naive BCR-activated clusters. Remarkably, some across most suggesting common programs may promote plasticity. Our study human provides understanding altered during alloantigen stimulation.