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Cited by 144T-cell and B-cell ImmunologyCytokine Signaling Pathways and InteractionsNF-κB Signaling Pathways

IL-21 and CD40L synergistically promote plasma cell differentiation through upregulation of Blimp-1 in human B cells

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Ding, B Belinda, Bi, Enguang, Chen, Hongshan, Yu, J Jessica, Ye, B Hilda·2013·The Journal of Immunology
DOI 10.4049/jimmunol.1201678PMC PMC3563840
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Abstract

After undergoing Ig somatic hypermutation and Ag selection, germinal center (GC) B cells terminally differentiate into either memory or plasma cells (PCs). It is known that the CD40L and IL-21/STAT3 signaling pathways play critical roles in this process, yet it is unclear how the B cell transcription program interprets and integrates these two types of T cell–derived signals. In this study, we characterized the role of STAT3 in the GC-associated PC differentiation using purified human tonsillar GC B cells and a GC B cell-like cell line. When primary GC B cells were cultured under PC differentiation condition, STAT3 inhibition by AG490 prevented the transition from GC centrocytes to preplasmablast, suggesting that STAT3 is required for the initiation of PC development. In a GC B cell-like human B cell line, although IL-21 alone can induce low-level Blimp-1 expression, maximum Blimp-1 upregulation and optimal PC differentiation required both IL-21 and CD40L. CD40L, although having no effect on Blimp-1 as a single agent, greatly augmented the amplitude and duration of IL-21–triggered Jak-STAT3 signaling. In the human PRDM1 locus, CD40L treatment enhanced the ability of STAT3 to upregulate Blimp-1 by removing BCL6, a potent inhibitor of Blimp-1 expression, from a shared BCL6/STAT3 site in intron 3. Thus, IL-21 and CD40L collaborate through at least two distinct mechanisms to synergistically promote Blimp-1 activation and PC differentiation.

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  • STAT3 controls development of CXCR5-expressing T follicular helper cells, their localization to the B cell follicle within germinal centers, and their IL-21 secretion, which mediates B cell help by stimulating proliferation and antibody affinity maturation.

    “STAT3 also controls development of CXC chemokine receptor 5–expressing T follicular helper cells, their localization to the B cell follicle within germinal centers of secondary lymphoid organs, and their IL-21 secretion, which mediates B cell help in germinal centers by stimulating proliferation and antibody affinity maturation”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Ding et al., 2013

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Cited by

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Authors
Ding, B. B., Bi, E., Chen, H., Yu, J. J., & Ye, B. H.
Affiliations
Albert Einstein College of Medicine (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2013-02
Volume
190
Issue
4
Pages
1827-1836
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1201678
PMC
PMC3563840
OpenAlex
W2139361228
Cited by
144
References
1
Citations by year
2026: 4 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 11 · 2021: 15 · 2020: 16 · 2019: 13 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 12 · 2014: 9 · 2013: 3
FWCI
6.27
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01 CA 85573, R01CA085573)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
IL-21, CD40 ligand, Blimp-1, plasma cell differentiation, germinal center B cells, STAT3 signaling, BCL6, tonsillar B cells
MeSH terms
Positive Regulatory Domain I-Binding Factor 1, Interleukin-21, Adjuvants, Immunologic, Cell Differentiation, Humans, Interleukins, Molecular Sequence Data, Organ Culture Techniques, Plasma Cells, Repressor Proteins, Palatine Tonsil, Up-Regulation, B-Lymphocyte Subsets, CD40 Ligand, Cell Line, Tumor, STAT3 Transcription Factor, Janus Kinases

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