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.
Bibliographical noteFunding Information:
This study was supported by National Institutes of Health grant R35CA-210105 (to R. Dalla-Favera) and funded in part through the NIH/NCI Cancer Center Support grant P30CA013696. This research used the resources of the Cancer Center Flow Core Facility (Columbia University), the Genomics and High Throughput Screening Shared Resource (Columbia University), and the Digital and Computational Pathology Laboratory in the Department of Pathology and Cell Biology at Columbia University Irving Medical Center.
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