Single-cell Analysis of Germinal-center B Cells Informs on Lymphoma Cell of Origin and Outcome

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2020 Jul 1

PMID 32603407

Citations 91

Authors

Antony B Holmes

Clarissa Corinaldesi

Qiong Shen

Rahul Kumar

Nicolo Compagno

Zhong Wang

Mor Nitzan

Eli Grunstein

Laura Pasqualucci

Riccardo Dalla-Favera

Katia Basso

Affiliations

Soon will be listed here.

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.

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References

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

Hauser A, Junt T, Mempel T, Sneddon M, Kleinstein S, Henrickson S . Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity. 2007; 26(5):655-67. DOI: 10.1016/j.immuni.2007.04.008. View

Ersching J, Efeyan A, Mesin L, Jacobsen J, Pasqual G, Grabiner B . Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase. Immunity. 2017; 46(6):1045-1058.e6. PMC: 5526448. DOI: 10.1016/j.immuni.2017.06.005. View

Stoeckius M, Hafemeister C, Stephenson W, Houck-Loomis B, Chattopadhyay P, Swerdlow H . Simultaneous epitope and transcriptome measurement in single cells. Nat Methods. 2017; 14(9):865-868. PMC: 5669064. DOI: 10.1038/nmeth.4380. View

Toth Z, Mezey E . Simultaneous visualization of multiple antigens with tyramide signal amplification using antibodies from the same species. J Histochem Cytochem. 2007; 55(6):545-54. DOI: 10.1369/jhc.6A7134.2007. View

Falini B, Fizzotti M, Pucciarini A, Bigerna B, Marafioti T, Gambacorta M . A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood. 2000; 95(6):2084-92. View

Milpied P, Cervera-Marzal I, Mollichella M, Tesson B, Brisou G, Traverse-Glehen A . Human germinal center transcriptional programs are de-synchronized in B cell lymphoma. Nat Immunol. 2018; 19(9):1013-1024. DOI: 10.1038/s41590-018-0181-4. View

Domeier P, Chodisetti S, Soni C, Schell S, Elias M, Wong E . IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity. J Exp Med. 2016; 213(5):715-32. PMC: 4854731. DOI: 10.1084/jem.20151722. View

Chapuy B, Stewart C, Dunford A, Kim J, Kamburov A, Redd R . Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018; 24(5):679-690. PMC: 6613387. DOI: 10.1038/s41591-018-0016-8. View

10.

Dominguez-Sola D, Kung J, Holmes A, Wells V, Mo T, Basso K . The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program. Immunity. 2015; 43(6):1064-74. DOI: 10.1016/j.immuni.2015.10.015. View

11.

Phan T, Paus D, Chan T, Turner M, Nutt S, Basten A . High affinity germinal center B cells are actively selected into the plasma cell compartment. J Exp Med. 2006; 203(11):2419-24. PMC: 2118125. DOI: 10.1084/jem.20061254. View

12.

Sha C, Barrans S, Cucco F, Bentley M, Care M, Cummin T . Molecular High-Grade B-Cell Lymphoma: Defining a Poor-Risk Group That Requires Different Approaches to Therapy. J Clin Oncol. 2018; 37(3):202-212. PMC: 6338391. DOI: 10.1200/JCO.18.01314. View

13.

Victora G, Dominguez-Sola D, Holmes A, Deroubaix S, Dalla-Favera R, Nussenzweig M . Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas. Blood. 2012; 120(11):2240-8. PMC: 3447782. DOI: 10.1182/blood-2012-03-415380. View

14.

Suan D, Krautler N, Maag J, Butt D, Bourne K, Hermes J . CCR6 Defines Memory B Cell Precursors in Mouse and Human Germinal Centers, Revealing Light-Zone Location and Predominant Low Antigen Affinity. Immunity. 2017; 47(6):1142-1153.e4. DOI: 10.1016/j.immuni.2017.11.022. View

15.

Pasqualucci L, Dalla-Favera R . Genetics of diffuse large B-cell lymphoma. Blood. 2018; 131(21):2307-2319. PMC: 5969374. DOI: 10.1182/blood-2017-11-764332. View

16.

Cattoretti G, Lin K, Calame K . Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J Immunol. 2000; 165(10):5462-71. DOI: 10.4049/jimmunol.165.10.5462. View

17.

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

18.

Rosenwald A, Wright G, Chan W, Connors J, Campo E, Fisher R . The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346(25):1937-47. DOI: 10.1056/NEJMoa012914. View

19.

Aiba Y, Yamazaki T, Okada T, Gotoh K, Sanjo H, Ogata M . BANK negatively regulates Akt activation and subsequent B cell responses. Immunity. 2006; 24(3):259-68. DOI: 10.1016/j.immuni.2006.01.002. View

20.

Michaelsen T, Richter J, Brondum R, Klapper W, Johnsen H, Albertsen M . A B-cell-associated gene signature classification of diffuse large B-cell lymphoma by NanoString technology. Blood Adv. 2018; 2(13):1542-1546. PMC: 6039667. DOI: 10.1182/bloodadvances.2018017988. View