Generation of a single-cell B cell atlas of antibody repertoires and transcriptomes to identify signatures associated with antigen specificity.
Immune response
Immunology
Transcriptomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
17 Mar 2023
17 Mar 2023
Historique:
received:
30
08
2022
revised:
07
12
2022
accepted:
20
01
2023
entrez:
28
2
2023
pubmed:
1
3
2023
medline:
1
3
2023
Statut:
epublish
Résumé
Although new genomics-based pipelines have potential to augment antibody discovery, these methods remain in their infancy due to an incomplete understanding of the selection process that governs B cell clonal selection, expansion, and antigen specificity. Furthermore, it remains unknown how factors such as aging and reduction of tolerance influence B cell selection. Here we perform single-cell sequencing of antibody repertoires and transcriptomes of murine B cells following immunizations with a model therapeutic antigen target. We determine the relationship between antibody repertoires, gene expression signatures, and antigen specificity across 100,000 B cells. Recombinant expression and characterization of 227 monoclonal antibodies revealed the existence of clonally expanded and class-switched antigen-specific B cells that were more frequent in young mice. Although integrating multiple repertoire features such as germline gene usage and transcriptional signatures failed to distinguish antigen-specific from nonspecific B cells, other features such as immunoglobulin G (IgG) subtype and sequence composition correlated with antigen specificity.
Identifiants
pubmed: 36852274
doi: 10.1016/j.isci.2023.106055
pii: S2589-0042(23)00132-3
pmc: PMC9958373
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106055Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
S.T.R. is a co-founder and holds shares of Engimmune Therapeutics AG. S.T.R. may hold shares of Alloy Therapeutics. S.T.R. is on the scientific advisory board of Engimmune Therapeutics and Alloy Therapeutics. T.C, D.S. and D.J.L. are or were employees of UCB Pharma. D.J.L. holds stock and/or stock options in UCB Pharma.
Références
J Immunol. 2003 Sep 1;171(5):2326-30
pubmed: 12928378
Cell Mol Life Sci. 2013 Oct;70(19):3603-16
pubmed: 23354061
Nat Rev Immunol. 2016 Oct;16(10):626-38
pubmed: 27546235
Gerontology. 2017;63(6):515-523
pubmed: 28768257
Vaccine. 2005 May 9;23(25):3232-5
pubmed: 15837226
Nat Biotechnol. 2010 Sep;28(9):965-9
pubmed: 20802495
Front Immunol. 2017 Dec 07;8:1745
pubmed: 29270179
Front Immunol. 2022 Feb 02;13:782441
pubmed: 35185882
Eur J Immunol. 2022 Feb;52(2):297-311
pubmed: 34727578
Lancet. 2021 Jan 9;397(10269):99-111
pubmed: 33306989
Cell. 2019 Dec 12;179(7):1636-1646.e15
pubmed: 31787378
Cell. 2020 Jul 9;182(1):73-84.e16
pubmed: 32425270
NAR Genom Bioinform. 2021 Apr 14;3(2):lqab023
pubmed: 33884369
Cell Rep. 2020 Jan 21;30(3):905-913.e6
pubmed: 31968262
Aging Cell. 2013 Apr;12(2):303-11
pubmed: 23410004
Expert Opin Ther Targets. 2019 Apr;23(4):295-307
pubmed: 30856027
Science. 2018 Dec 14;362(6420):1306-1309
pubmed: 30545888
Sci Adv. 2020 Jul 29;6(31):eabb0806
pubmed: 32832688
J Virol. 2012 Mar;86(6):2911-8
pubmed: 22238318
JCI Insight. 2017 May 4;2(9):
pubmed: 28469084
Am J Trop Med Hyg. 2022 Feb 7;:
pubmed: 35130487
Vaccine. 2016 Dec 20;34(52):6655-6664
pubmed: 27769596
Nat Commun. 2016 Aug 17;7:12535
pubmed: 27531490
Nat Biotechnol. 2005 Sep;23(9):1105-16
pubmed: 16151404
MAbs. 2019 Jul;11(5):870-883
pubmed: 30898066
Bioinformatics. 2017 Nov 15;33(22):3645-3647
pubmed: 29036507
Oncogene. 2006 Aug 10;25(35):4923-36
pubmed: 16532022
Trans R Soc Trop Med Hyg. 2015 Jan;109(1):9-15
pubmed: 25573105
Cell Immunol. 2001 Dec 15;214(2):99-109
pubmed: 12088409
Elife. 2020 Mar 24;9:
pubmed: 32204792
Mech Ageing Dev. 2009 Oct;130(10):681-90
pubmed: 19698733
Nat Protoc. 2018 Jan;13(1):99-117
pubmed: 29240734
Immunity. 2004 Jul;21(1):81-93
pubmed: 15345222
Nat Commun. 2019 Jul 16;10(1):3120
pubmed: 31311926
J Clin Invest. 2011 Aug;121(8):3109-19
pubmed: 21785218
Nat Rev Immunol. 2015 Mar;15(3):160-71
pubmed: 25698678
Blood. 2011 Aug 4;118(5):1305-15
pubmed: 21543762
Front Immunol. 2013 May 29;4:128
pubmed: 23755051
Front Immunol. 2021 Mar 08;12:612747
pubmed: 33763063
Commun Biol. 2019 Aug 9;2:304
pubmed: 31428692
Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2113766119
pubmed: 35486691
Cell Rep. 2021 Jun 22;35(12):109286
pubmed: 34161770
J Biol Chem. 2004 Mar 12;279(11):10228-36
pubmed: 14670953
Sci Rep. 2015 Sep 10;5:13926
pubmed: 26355042
Immunology. 2018 Jan;153(1):31-41
pubmed: 28898398
Nature. 2020 Oct;586(7827):127-132
pubmed: 32866963
Nat Biotechnol. 2022 Aug;40(8):1270-1275
pubmed: 35241839
Annu Rev Immunol. 2016 May 20;34:635-59
pubmed: 27168247
Cell Rep. 2022 Jan 18;38(3):110242
pubmed: 34998467
Nat Med. 2015 Jan;21(1):86-91
pubmed: 25501908
Rejuvenation Res. 2006 Spring;9(1):117-25
pubmed: 16608408
Nat Rev Immunol. 2012 Oct;12(10):709-19
pubmed: 23007571
Proc Biol Sci. 2021 Feb 24;288(1945):20202793
pubmed: 33622131
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Cell Rep. 2020 Jan 28;30(4):997-1012.e6
pubmed: 31995768
J Exp Med. 2009 Sep 28;206(10):2151-9
pubmed: 19752183
Cell Rep. 2022 Nov 8;41(6):111613
pubmed: 36351385
Vaccines (Basel). 2021 Mar 20;9(3):
pubmed: 33804604
Nat Rev Cancer. 2015 Jun;15(6):361-70
pubmed: 25998715
Vaccine. 2010 Feb 3;28(5):1226-33
pubmed: 19945415
Haematologica. 2010 Dec;95(12):2056-62
pubmed: 20823132
J Immunol. 2006 Jan 15;176(2):1007-12
pubmed: 16393987
Front Immunol. 2018 Mar 12;9:380
pubmed: 29593710
Arthritis Res Ther. 2009;11(2):R40
pubmed: 19291304
Nat Biotechnol. 2018 Jan;36(1):20-30
pubmed: 29251730
Nat Methods. 2019 Jan;16(1):59-62
pubmed: 30559431
Nat Biotechnol. 2013 Feb;31(2):166-9
pubmed: 23334449
J Immunol. 2003 Feb 1;170(3):1267-73
pubmed: 12538685
Cell Rep. 2022 May 31;39(9):110901
pubmed: 35649357
Int Immunol. 2006 Jan;18(1):31-9
pubmed: 16291657
Aging (Albany NY). 2011 Apr;3(4):438-43
pubmed: 21483035
Cell Discov. 2020 May 4;6:31
pubmed: 32377375
MAbs. 2019 Nov-Dec;11(8):1367-1380
pubmed: 31478465
Emerg Microbes Infect. 2016 Apr 06;5:e33
pubmed: 27048742
J Immunol. 2004 Feb 15;172(4):2155-62
pubmed: 14764681
Nat Clin Pract Rheumatol. 2008 Sep;4(9):491-8
pubmed: 18756274
Clin Exp Immunol. 2016 Jan;183(1):50-6
pubmed: 26332693
PLoS One. 2012;7(3):e34145
pubmed: 22461903
Aging Cell. 2009 Feb;8(1):18-25
pubmed: 18986373
Immunol Rev. 1997 Dec;160:63-77
pubmed: 9476666
J Infect Dis. 1999 Jan;179(1):31-6
pubmed: 9841819
Front Cell Dev Biol. 2020 May 26;8:401
pubmed: 32528961
Front Immunol. 2018 Feb 21;9:224
pubmed: 29515569
Nat Biotechnol. 2015 May;33(5):495-502
pubmed: 25867923