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PD-1 is a novel regulator of human B-cell activation
Abstract
The outcome of the adaptive immune response is determined by the integration of both positive and negative signals, respectively, induced upon the triggering of co-signaling receptors. One of them, programmed cell death 1 (PDCD1/PD-1) has largely been shown to be involved in the negative regulation of T-cell activation. However, PD-1 is also expressed on human B cells, and its role(s) in the process of human B-cell activation remains uncertain thus far. In this study, we describe the expression of PD-1 on the major human B-cells subsets isolated from peripheral blood and lymph nodes. We showed that PD-1 was expressed on naive B cells, was differentially expressed on peripheral IgM memory as compared with memory B cells and was lost on germinal center B cells. Expression of PD-1 ligands (PD-Ls) was induced by TLR9 activation. Finally, we showed that PD-1 was recruited to the B-cell receptor upon triggering. We determined that during TLR9 activation, blockade of PD-1/PD-Ls pathways indeed increased B-cell activation, proliferation and the production of inflammatory cytokines. Altogether, our results show, that, as reported in T cells, PD-1/PD-Ls complexes acted as inhibitors of the B-cell activation cascade and highlight the importance of devising future therapies able to modulate lymphocyte activation through the targeting of the PD-1/PD-Ls pathways.
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“Since other cell types (such as dendritic cells and B cells) can also be influenced by PD-1 signaling, inhibition of the PD-1/PD-L1 pathway may also have T cell-independent effects, whose impact on immune responses during checkpoint inhibitor therapy remain to be elucidated (36, 58).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [36]
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Metadata
- Authors
- Thibult, M.-L., Mamessier, E., Gertner-Dardenne, J., Pastor, S., Just-Landi, S., Xerri, L., Chetaille, B., & Olive, D.
- Affiliations
- Inserm (FR)
- Centre de Recherche en Cancérologie de Marseille (FR)
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-18
- Volume
- 25
- Issue
- 2
- Pages
- 129-137
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2131640081
- Cited by
- 365
- References
- 45
- Citations by year
- 2026: 16 · 2025: 28 · 2024: 38 · 2023: 25 · 2022: 44 · 2021: 43 · 2020: 47 · 2019: 38 · 2018: 27 · 2017: 20 · 2016: 19 · 2015: 8 · 2014: 8 · 2013: 4
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- PD-1, PD-L1, PD-L2, B cell activation, B cell receptor signaling, TLR9, naive B cells, memory B cells, germinal center B cells, B cell proliferation, inflammatory cytokines
- MeSH terms
- B-Lymphocytes, Humans, Lymphocyte Activation, Programmed Cell Death 1 Receptor
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