Single-cell analysis of germinal-center B cells informs on lymphoma cell of origin and outcome
Antony B. Holmes, Clarissa Corinaldesi, Qiong Shen, Rahul Kumar, Nicolò Compagno, Zhong Wang, Mor Nitzan, Eli Grunstein, Laura Pasqualucci, Riccardo Dalla‐Favera, Katia Basso
Abstract
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.