Antibody Repertoire Analysis of Tumor-Infiltrating B Cells Reveals Distinct Signatures and Distributions Across Tissues.
Animals
Antibody Diversity
B-Lymphocyte Subsets
/ immunology
Blood Cells
/ immunology
Bone Marrow
/ pathology
Cell Line, Tumor
/ transplantation
Cell Movement
Female
High-Throughput Nucleotide Sequencing
Humans
Immunoglobulin G
/ genetics
Immunoglobulin Heavy Chains
/ genetics
Immunoglobulin M
/ genetics
Immunoglobulin Variable Region
/ genetics
Lymph Nodes
/ pathology
Lymphocytes, Tumor-Infiltrating
/ immunology
Mammary Neoplasms, Experimental
/ immunology
Mice
Mice, Inbred BALB C
Organ Specificity
Receptors, Antigen, B-Cell
/ genetics
Somatic Hypermutation, Immunoglobulin
Triple Negative Breast Neoplasms
/ immunology
Tumor Microenvironment
/ immunology
AIRR-seq
B cell
BCR-Seq
VDJ recombination
antibody repertoire
next generation sequencing
triple negative breast cancer
tumor infiltrating lymphocytes
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
05
2021
accepted:
29
06
2021
entrez:
5
8
2021
pubmed:
6
8
2021
medline:
21
12
2021
Statut:
epublish
Résumé
The role of B cells in the tumor microenvironment (TME) has largely been under investigated, and data regarding the antibody repertoire encoded by B cells in the TME and the adjacent lymphoid organs are scarce. Here, we utilized B cell receptor high-throughput sequencing (BCR-Seq) to profile the antibody repertoire signature of tumor-infiltrating lymphocyte B cells (TIL-Bs) in comparison to B cells from three anatomic compartments in a mouse model of triple-negative breast cancer. We found that TIL-Bs exhibit distinct antibody repertoire measures, including high clonal polarization and elevated somatic hypermutation rates, suggesting a local antigen-driven B-cell response. Importantly, TIL-Bs were highly mutated but non-class switched, suggesting that class-switch recombination may be inhibited in the TME. Tracing the distribution of TIL-B clones across various compartments indicated that they migrate to and from the TME. The data thus suggests that antibody repertoire signatures can serve as indicators for identifying tumor-reactive B cells.
Identifiants
pubmed: 34349765
doi: 10.3389/fimmu.2021.705381
pmc: PMC8327180
doi:
Substances chimiques
Immunoglobulin G
0
Immunoglobulin Heavy Chains
0
Immunoglobulin M
0
Immunoglobulin Variable Region
0
Receptors, Antigen, B-Cell
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
705381Informations de copyright
Copyright © 2021 Aizik, Dror, Taussig, Barzel, Carmi and Wine.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Oncoimmunology. 2013 Jul 1;2(7):e25443
pubmed: 24073382
J Exp Med. 2013 Mar 11;210(3):457-64
pubmed: 23420879
Cancer Res. 2003 Jun 15;63(12):3275-80
pubmed: 12810659
Cell Mol Immunol. 2019 Jan;16(1):6-18
pubmed: 29628498
Cell. 2017 May 4;169(4):750-765.e17
pubmed: 28475900
J Biol Chem. 2020 Jul 17;295(29):9823-9837
pubmed: 32409582
J Immunol. 2010 Apr 1;184(7):4006-16
pubmed: 20194720
Eur J Immunol. 1981 Dec;11(12):1012-6
pubmed: 7327198
Cell Death Dis. 2018 Jan 25;9(2):109
pubmed: 29371592
Nat Biotechnol. 2017 Oct 11;35(10):908-911
pubmed: 29020005
Front Immunol. 2018 Mar 14;9:462
pubmed: 29593723
Cancer Immunol Res. 2017 Oct;5(10):898-907
pubmed: 28848053
Nature. 2019 Oct;574(7776):122-126
pubmed: 31554970
Immunol Today. 1993 Jan;14(1):15-7
pubmed: 8442856
Trends Cancer. 2016 Dec;2(12):747-757
pubmed: 28626801
Cell Rep. 2021 Mar 16;34(11):108856
pubmed: 33730590
Clin Cancer Res. 2014 Jul 15;20(14):3818-29
pubmed: 24916698
Cytometry B Clin Cytom. 2010;78 Suppl 1:S47-60
pubmed: 20839338
Front Immunol. 2018 Feb 01;9:117
pubmed: 29449843
Immunity. 2019 Aug 20;51(2):337-350.e7
pubmed: 31375460
J Mol Biol. 1997 Nov 7;273(4):927-48
pubmed: 9367782
Front Immunol. 2017 Jun 30;8:767
pubmed: 28713385
Clin Vaccine Immunol. 2011 Nov;18(11):1951-6
pubmed: 21880858
Eur J Immunol. 2015 Apr;45(4):999-1009
pubmed: 25545618
Cancer Res. 2006 Aug 1;66(15):7741-7
pubmed: 16885377
Nat Methods. 2015 May;12(5):380-1
pubmed: 25924071
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8
pubmed: 18503082
Cell Rep. 2017 May 16;19(7):1467-1478
pubmed: 28514665
Cell. 2017 May 4;169(4):736-749.e18
pubmed: 28475899
Nat Commun. 2019 Mar 21;10(1):1321
pubmed: 30899025
Mol Immunol. 2007 Feb;44(6):1057-64
pubmed: 16930714
Bioinformatics. 2014 Oct;30(19):2811-2
pubmed: 24930139
Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):653-65
pubmed: 19008195
Cancers (Basel). 2019 Jun 04;11(6):
pubmed: 31167511
Oncotarget. 2016 Aug 23;7(34):55828-55839
pubmed: 27331871
Mol Cell. 2019 May 2;74(3):584-597.e9
pubmed: 30905508
Clin Cancer Res. 2016 Jun 15;22(12):3005-15
pubmed: 26763251
Nat Commun. 2017 May 05;8:15081
pubmed: 28474673
Science. 2005 Dec 2;310(5753):1510-2
pubmed: 16322460
Cancer Res. 2012 Aug 15;72(16):3997-4007
pubmed: 22850419
Tumour Biol. 2016 May;37(5):6581-8
pubmed: 26638169
Br J Cancer. 2013 Sep 17;109(6):1676-84
pubmed: 23982600
Annu Rev Immunol. 2002;20:165-96
pubmed: 11861601
Nature. 2020 Jan;577(7791):561-565
pubmed: 31942071
Cell Rep. 2017 Jan 3;18(1):248-262
pubmed: 28052254
PLoS One. 2018 Jul 5;13(7):e0199034
pubmed: 29975708
Eur J Immunol. 2009 Aug;39(8):2095-9
pubmed: 19637201
Front Immunol. 2018 Jul 30;9:1686
pubmed: 30105017
Cancer Immunol Immunother. 2018 May;67(5):729-738
pubmed: 29427082
Nat Biotechnol. 2014 Feb;32(2):158-68
pubmed: 24441474
J Immunol. 2002 Aug 15;169(4):1829-36
pubmed: 12165506
Oncotarget. 2016 Sep 13;7(37):60461-60474
pubmed: 27528023
Annu Rev Immunol. 1989;7:145-73
pubmed: 2523712
Immunity. 2000 Jul;13(1):37-45
pubmed: 10933393
J Immunol. 2009 Sep 1;183(5):3195-203
pubmed: 19667089
Front Microbiol. 2019 Oct 23;10:2407
pubmed: 31708888
BMC Immunol. 2014 Oct 16;15:40
pubmed: 25318652
Front Immunol. 2018 Nov 16;9:2673
pubmed: 30505309
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10662-7
pubmed: 21670304
BMC Infect Dis. 2015 Jul 21;15:276
pubmed: 26193930
Cell. 2002 Apr;109 Suppl:S45-55
pubmed: 11983152
Clin Cancer Res. 2012 Jun 15;18(12):3281-92
pubmed: 22553348