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

被引:124
作者
Holmes, Antony B. [1 ]
Corinaldesi, Clarissa [1 ]
Shen, Qiong [1 ]
Kumar, Rahul [1 ]
Compagno, Nicolo [1 ]
Wang, Zhong [2 ]
Nitzan, Mor [7 ]
Grunstein, Eli [3 ]
Pasqualucci, Laura [1 ,2 ,6 ]
Dalla-Favera, Riccardo [1 ,2 ,4 ,5 ,6 ]
Basso, Katia [1 ,2 ]
机构
[1] Columbia Univ, Inst Canc Genet, New York, NY 10027 USA
[2] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA
[3] Columbia Univ, Dept Otolaryngol Head & Neck Surg, New York, NY USA
[4] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10027 USA
[5] Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA
[6] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA
[7] Harvard Univ, Cambridge, MA 02138 USA
基金
美国国家卫生研究院;
关键词
PLASMA-CELL; MEMORY B; TYROSINE PHOSPHORYLATION; CENTER SELECTION; CENTER LIGHT; CENTER DARK; IFN-GAMMA; EXPRESSION; DYNAMICS; TRANSCRIPTION;
D O I
10.1084/jem.20200483
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 similar to 80% of diffuse large B cell lymphomas (DLBCLs) and identified novel prognostic subgroups of DLBCL.
引用
收藏
页数:26
相关论文
共 70 条
[1]   BANK negatively regulates Akt activation and subsequent B cell responses [J].
Aiba, Y ;
Yamazaki, T ;
Okada, T ;
Gotoh, K ;
Sanjo, H ;
Ogata, M ;
Kurosaki, T .
IMMUNITY, 2006, 24 (03) :259-268
[2]   Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].
Alizadeh, AA ;
Eisen, MB ;
Davis, RE ;
Ma, C ;
Lossos, IS ;
Rosenwald, A ;
Boldrick, JG ;
Sabet, H ;
Tran, T ;
Yu, X ;
Powell, JI ;
Yang, LM ;
Marti, GE ;
Moore, T ;
Hudson, J ;
Lu, LS ;
Lewis, DB ;
Tibshirani, R ;
Sherlock, G ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Warnke, R ;
Levy, R ;
Wilson, W ;
Grever, MR ;
Byrd, JC ;
Botstein, D ;
Brown, PO ;
Staudt, LM .
NATURE, 2000, 403 (6769) :503-511
[3]   Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5 [J].
Allen, CDC ;
Ansel, KM ;
Low, C ;
Lesley, R ;
Tamamura, H ;
Fujii, N ;
Cyster, JG .
NATURE IMMUNOLOGY, 2004, 5 (09) :943-952
[4]   Imaging of germinal center selection events during affinity maturation [J].
Allen, Christopher D. C. ;
Okada, Takaharu ;
Tang, H. Lucy ;
Cyster, Jason G. .
SCIENCE, 2007, 315 (5811) :528-531
[5]   Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo [J].
Angelin-Duclos, C ;
Cattoretti, G ;
Lin, KI ;
Calame, K .
JOURNAL OF IMMUNOLOGY, 2000, 165 (10) :5462-5471
[6]   Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma [J].
Arthur, Sarah E. ;
Jiang, Aixiang ;
Grande, Bruno M. ;
Alcaide, Miguel ;
Cojocaru, Razvan ;
Rushton, Christopher K. ;
Mottok, Anja ;
Hilton, Laura K. ;
Lat, Prince Kumar ;
Zhao, Eric Y. ;
Culibrk, Luka ;
Ennishi, Daisuke ;
Jessa, Selin ;
Chong, Lauren ;
Thomas, Nicole ;
Pararajalingam, Prasath ;
Meissner, Barbara ;
Boyle, Merrill ;
Davidson, Jordan ;
Bushell, Kevin R. ;
Lai, Daniel ;
Farinha, Pedro ;
Slack, Graham W. ;
Morin, Gregg B. ;
Shah, Sohrab ;
Sen, Dipankar ;
Jones, Steven J. M. ;
Mungall, Andrew J. ;
Gascoyne, Randy D. ;
Audas, Timothy E. ;
Unrau, Peter ;
Marra, Marco A. ;
Connors, Joseph M. ;
Steidl, Christian ;
Scott, David W. ;
Morin, Ryan D. .
NATURE COMMUNICATIONS, 2018, 9
[7]   B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans [J].
Avery, Danielle T. ;
Deenick, Elissa K. ;
Ma, Cindy S. ;
Suryani, Santi ;
Simpson, Nicholas ;
Chew, Gary Y. ;
Chan, Tyani D. ;
Palendira, Umamainthan ;
Bustamante, Jacinta ;
Boisson-Dupuis, Stephanie ;
Choo, Sharon ;
Bleasel, Karl E. ;
Peake, Jane ;
King, Cecile ;
French, Martyn A. ;
Engelhard, Dan ;
Al-Hajjar, Sami ;
Al-Muhsen, Saleh ;
Magdorf, Klaus ;
Roesler, Joachim ;
Arkwright, Peter D. ;
Hissaria, Pravin ;
Riminton, D. Sean ;
Wong, Melanie ;
Brink, Robert ;
Fulcher, David A. ;
Casanova, Jean-Laurent ;
Cook, Matthew C. ;
Tangye, Stuart G. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (01) :155-171
[8]   Germinal centres and B cell lymphomagenesis [J].
Basso, Katia ;
Dalla-Favera, Riccardo .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (03) :172-184
[9]   Roles of BCL6 in normal and transformed germinal center B cells [J].
Basso, Katia ;
Dalla-Favera, Riccardo .
IMMUNOLOGICAL REVIEWS, 2012, 247 :172-183
[10]   Dimensionality reduction for visualizing single-cell data using UMAP [J].
Becht, Etienne ;
McInnes, Leland ;
Healy, John ;
Dutertre, Charles-Antoine ;
Kwok, Immanuel W. H. ;
Ng, Lai Guan ;
Ginhoux, Florent ;
Newell, Evan W. .
NATURE BIOTECHNOLOGY, 2019, 37 (01) :38-+