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Updated: Aug 29, 2026
Murine Model of CD40-activation of B cells
Published on: March 5, 2010
Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation
1Department of Immunology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. hnakano@med.juntendo.ac.jp
Abstract:
TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-kappaB and c-Jun NH(2)-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-beta receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-kappaB or c-Jun NH(2)-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5(-/-) mice. However, traf5(-/-) B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5(-/-) T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signaling.
Insights
Tumor necrosis factor receptor-associated factor 5 (TRAF5) plays a key role in CD40 and CD27 signaling. TRAF5 deficiency impairs B cell proliferation and T cell costimulation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Tumor necrosis factor receptor-associated factor 5 (TRAF5) is involved in signaling pathways activated by the TNF receptor superfamily.
- TRAF5 mediates activation of NF-kappaB and c-Jun NH(2)-terminal kinase/stress-activated protein kinase.
- Members of the TNF receptor superfamily include CD27, CD30, CD40, and lymphotoxin-beta receptor.
Purpose of the Study:
- To investigate the in vivo function of TRAF5.
- To determine the role of TRAF5 in immune cell signaling and function.
Main Methods:
- Gene targeting was used to generate TRAF5-deficient (traf5(-/-)) mice.
- Analysis of NF-kappaB and c-Jun NH(2)-terminal kinase/stress-activated protein kinase activation.
- Assessment of B cell proliferation, surface molecule expression (CD23, CD54, CD80, CD86, Fas), and immunoglobulin (Ig) production in response to CD40 stimulation.
- Evaluation of CD27-mediated costimulatory signals in T cells.
Main Results:
- TRAF5 deficiency did not abrogate NF-kappaB or c-Jun NH(2)-terminal kinase/stress-activated protein kinase activation by TNF, CD27, or CD40.
- traf5(-/-) B cells exhibited defects in proliferation and surface molecule upregulation upon CD40 stimulation.
- In vitro Ig production by traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was significantly reduced.
- CD27-mediated costimulatory signaling was impaired in traf5(-/-) T cells.
Conclusions:
- TRAF5 is essential for CD40-mediated B cell responses, including proliferation and Ig production.
- TRAF5 plays a critical role in CD27-mediated costimulatory signaling in T cells.
- These findings highlight the specific involvement of TRAF5 in CD40 and CD27 signaling pathways in vivo.
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