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

Poe, Jonathan C

Fang, Jiyuan

Zhang, Dadong

Lee, Marissa R

DiCioccio, Rachel A

Su, Hsuan

Qin, Xiaodi

Zhang, Jennifer Y

Visentin, Jonathan

Bracken, Sonali J

Ho, Vincent T

Wang, Kathy S

Rose, Jeremy J

Pavletic, Steven Z

Hakim, Frances T

Jia, Wei

Suthers, Amy N

Curry-Chisolm, Itaevia M

Horwitz, Mitchell E

Rizzieri, David A

McManigle, William C

Chao, Nelson J

Cardones, Adela R

Xie, Jichun

Owzar, Kouros

Sarantopoulos, Stefanie

2024-07-16T15:43:06Z

2024-07-16T15:43:06Z

2023-06

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.

169732

2379-3708

2379-3708

https://hdl.handle.net/10161/31277

eng

American Society for Clinical Investigation

JCI insight

10.1172/jci.insight.169732

https://creativecommons.org/licenses/by-nc/4.0

B-Lymphocytes

Humans

Graft vs Host Disease

Receptors, Antigen, B-Cell

Hematopoietic Stem Cell Transplantation

Bronchiolitis Obliterans Syndrome

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

Journal article

Zhang, Jennifer Y|0000-0002-4485-1750

Bracken, Sonali J|0000-0003-1814-4099

Horwitz, Mitchell E|0000-0001-9863-8464

Chao, Nelson J|0000-0001-6725-7220

Xie, Jichun|0000-0001-5905-6728

e169732

11

Duke

School of Medicine

Staff

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Biostatistics & Bioinformatics

Integrative Immunobiology

Dermatology

Medicine

Pathology

Medicine, Rheumatology and Immunology

Duke Cancer Institute

University Institutes and Centers

Duke Global Health Institute

Duke Regeneration Center

Medicine, Hematologic Malignancies and Cellular Therapy

Biostatistics & Bioinformatics, Division of Integrative Genomics

Published

8