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Cited by 40T-cell and B-cell ImmunologyNF-κB Signaling PathwaysImmune Response and Inflammation

Syk mediates BCR- and CD40-signaling integration during B cell activation

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Ying, Haiyan, Li, Zhenping, Yang, Lifen, Zhang, Jian·2011·Immunobiology
DOI 10.1016/j.imbio.2010.09.016PMC PMC3075491
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Abstract

CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation. We found that spleen tyrosine kinase (Syk) is involved in CD40 signaling, and is synergistically activated in B cells in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk, and significantly enhances BCR-induced formation of complex consisting of, Vav-2, Btk, BLNK, and phospholipase C-gamma2 (PLC-γ2) leading to activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase, Akt, and NF-κB required for optimal B cell activation. Therefore, our data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively modify BCR signaling during B cell activation.

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  • Alternative signaling pathways through CD38, CD40, IL-4R, LPS/TLR4/MyD88, and CD86 also utilize PLCγ2, while TGF-βR stimulation inhibits PLCγ2 function in B cells.

    “Aside from BCR engagement, there are alternative signaling pathways initiated through extracellular immunological receptors that also utilize PLCγ2 to function, which include CD38 (16), CD40 (52), IL-4R (53, 54, 55) and the LPS/TLR4/MyD88 pathway, the latter of which induces ERK and NK-κB phosphorylation in MEKs in a PI3K-independent fashion (56). CD86 engagement was also observed to signal via PL”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [52]

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Authors
Ying, H., Li, Z., Yang, L., & Zhang, J.
Affiliations
University of Chicago (US)
Corresponding author
Zhang, Jian
ORCID
Venue
Immunobiology
Publisher
Elsevier BV
Published
2011-05
Volume
216
Issue
5
Pages
566-570
ISSN
0171-2985 (ISSN-L)
DOI
10.1016/j.imbio.2010.09.016
PMC
PMC3075491
OpenAlex
W2087154633
Cited by
40
References
44
Citations by year
2026: 1 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 3 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 3
FWCI
1.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • American Lung Association
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01AI090901)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
Syk, CD40 signaling, B cell receptor signaling, B cell activation, costimulation, Bruton's tyrosine kinase, PLCγ2, ERK, p38 MAPK, Akt, NF-κB
MeSH terms
Syk Kinase, Agammaglobulinaemia Tyrosine Kinase, Animals, B-Lymphocytes, Cells, Cultured, Female, Lymphocyte Activation, Mice, Inbred BALB C, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Signal Transduction, NF-kappa B, CD40 Antigens, Receptor Cross-Talk, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, Proto-Oncogene Proteins c-vav, Phospholipase C gamma

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