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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

Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in

Bruce S Hostager1, Sokol A Haxhinasto, Sarah L Rowland

  • 1Department of Pediatrics, Interdisciplinary Program in Immunology, University of Iowa, Iowa City 52242, USA.

The Journal of Biological Chemistry
|September 6, 2003
PubMed

Insights

Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays key roles in B cell signaling, including synergy with CD40 and B cell antigen receptor signals. TRAF2 also impacts IgM production and NF-kappaB activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Tumor necrosis factor receptor-associated factor (TRAF) proteins are crucial adapters in signaling pathways initiated by numerous receptors, including CD40.
  • Understanding individual TRAF functions is challenging due to experimental model limitations and poor viability of TRAF-deficient organisms.

Purpose of the Study:

  • To elucidate novel roles of TRAF2 in CD40 signaling using a novel homologous recombination system in B cell lines.
  • To investigate TRAF2's involvement in CD40-mediated B cell responses, including receptor signal synergy and immunoglobulin production.

Main Methods:

  • Development of B cell lines deficient in TRAF2 using a novel homologous recombination system.
  • Analysis of CD40 signaling pathways, including receptor synergy, IgM production, TRAF3 degradation, NF-kappaB activation, and CD80 up-regulation.

Main Results:

  • TRAF2 deficiency revealed new roles in the synergy between CD40 and B cell antigen receptor signals.
  • TRAF2 was found to be essential for CD40-mediated, TNF-dependent IgM production and participates in TRAF3 degradation during CD40 signaling.
  • TRAF2 and TRAF6 exhibit overlapping functions in CD40-mediated NF-kappaB activation and CD80 up-regulation.

Conclusions:

  • TRAF2 plays previously unappreciated roles in signaling by TNF receptor family members, particularly in B cell immune responses.
  • The novel experimental approach facilitates the analysis of genes critical for organism viability, advancing the study of TRAF family functions.

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