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Murine Model of CD40-activation of B cells
12:24

Murine Model of CD40-activation of B cells

Published on: March 6, 2010

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
PubMed

Insights

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.

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