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Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B
I Berberich1, G L Shu, E A Clark
1Department of Microbiology, University of Washington, Seattle 98195.
Journal of Immunology (Baltimore, Md. : 1950)
|November 15, 1994
Summary
CD40 cross-linking rapidly activates nuclear factor-kappa B (NF-kappa B) via tyrosine kinases in B cells. This activation influences gene expression, revealing NF-kappa B as a key intermediate in CD40 signaling pathways.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- CD40 is a B cell surface molecule regulating immune responses.
- CD40 engagement triggers B cell adhesion, IL-6 production, and Ig isotype switching.
- Early signaling events linking CD40 engagement to cellular responses remain poorly understood.
Purpose of the Study:
- To investigate the early molecular events following CD40 cross-linking.
- To determine the role of transcription factors in CD40-mediated signaling.
- To elucidate the pathway linking CD40 engagement to B cell gene expression.
Main Methods:
- Cross-linking of CD40 on human tonsillar B cells and B cell lines.
- Electrophoretic mobility shift assays (EMSA) to detect transcription factor activation.
- Transient transfection assays to assess NF-kappa B-dependent gene expression.
Main Results:
- CD40 cross-linking rapidly activates nuclear factor-kappa B (NF-kappa B) and related transcription factors.
- This activation is dependent on tyrosine kinase activity.
- NF-kappa B complexes contain p50, p65 (RelA), and c-Rel.
- CD40 engagement enhances NF-kappa B-dependent gene expression.
Conclusions:
- NF-kappa B acts as an intermediate signaling event in the CD40 pathway.
- The CD40 signaling pathway modulates the expression of B cell genes containing NF-kappa B sites.