Single-cell analysis of germinal-center B cells informs on lymphoma cell of origin and outcome

• Published in: The Journal of experimental medicine Vol. 217; no. 10
• Main Authors: Holmes, Antony B., Corinaldesi, Clarissa, Shen, Qiong, Kumar, Rahul, Compagno, Nicolo, Wang, Zhong, Nitzan, Mor, Grunstein, Eli, Pasqualucci, Laura, Dalla-Favera, Riccardo, Basso, Katia
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.10.2020
• Subjects: B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Cell Lineage; Fluorescent Antibody Technique; Gene Expression Profiling; Germinal Center - metabolism; Germinal Center - pathology; Humans; Leukemia & Lymphoma; Lymphoma - metabolism; Lymphoma - pathology; Single-Cell Analysis
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20200483

In response to T cell–dependent antigens, mature B cells are stimulated to form germinal centers (GCs), the sites of B cell affinity maturation and the cell of origin (COO) of most B cell lymphomas. To explore the dynamics of GC B cell development beyond the known dark zone and light zone compartments, we performed single-cell (sc) transcriptomic analysis on human GC B cells and identified multiple functionally linked subpopulations, including the distinct precursors of memory B cells and plasma cells. The gene expression signatures associated with these GC subpopulations were effective in providing a sc-COO for ∼80% of diffuse large B cell lymphomas (DLBCLs) and identified novel prognostic subgroups of DLBCL.