B Cell Receptor (BCR) Cross-Talk: IL-4 Creates an Alternate Pathway for BCR-Induced ERK Activation That Is Phosphatidylinositol 3-Kinase Independent
Open accessAbstract
IL-4 has pleiotropic effects on B cells. These effects include alteration of subsequent BCR-triggered responses. To identify a molecular basis for this receptor cross-talk, we examined ERK activation and NF-κB induction. We found that treatment with IL-4, but not other cytokines, affected subsequent BCR signaling by creating a new pathway in which the need for PI3K in ERK activation was eliminated. In contrast, the need for PI3K in NF-κB induction was not altered. The new pathway for ERK required time to develop, depended on STAT6, and was blocked by inhibition of macromolecular synthesis. As in the classical pathway, BCR-induced ERK activation in the new, PI3K-independent pathway required MEK and was reflected in c-Raf. Thus, IL-4 promotes an alternate pathway through which BCR is coupled to Raf/MEK/ERK that may function to heighten the responsiveness of B cells during times of immunological stress.
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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 [55]
The claim attributes PLCγ2 use to the IL-4R-associated alternative pathway. The Discussion (page unavailable) says instead that IL-4 treatment creates an alternative pathway for BCR-induced ERK activation that operates independently of PLCγ2; the Results section on PLC independence likewise says IL-4 eliminates the requirement for PLCγ2. This paper does not establish the other receptor pathways listed in the claim. (LLM, conf=0.88)
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- Authors
- Guo, B., & Rothstein, T. L.
- Affiliations
- Boston University (US)
- Corresponding author
- Guo, Benchang
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-05-01
- Volume
- 174
- Issue
- 9
- Pages
- 5375-5381
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1894411297
- Cited by
- 31
- References
- 54
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2018: 2 · 2016: 2 · 2014: 1 · 2013: 3
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service
- National Institute of Allergy and Infectious Diseases (AI-40181)
- 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
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- B cell receptor signaling, IL-4, ERK activation, Raf/MEK/ERK pathway, STAT6, receptor cross-talk, immune stress
- MeSH terms
- Animals, B-Lymphocytes, Cells, Cultured, Enzyme Activation, Male, Mice, Inbred BALB C, Mice, Transgenic, Phosphorylation, Receptors, Antigen, B-Cell, Signal Transduction, Trans-Activators, Interleukin-4, NF-kappa B, Mice, Knockout, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-raf, Mitogen-Activated Protein Kinase 1, Receptor Cross-Talk, Extracellular Signal-Regulated MAP Kinases, STAT6 Transcription Factor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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