The Binding Site for TRAF2 and TRAF3 but Not for TRAF6 Is Essential for CD40-Mediated Immunoglobulin Class Switching

Haifa H. Jabara, Dhafer Laouini, Erdyni Tsitsikov, Emiko Mizoguchi, Atul K. Bhan, Emanuela Castigli, Fatma Dedeoglu, Vadim Pivniouk, Scott R. Brodeur, Raif S. Geha

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

To define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40ΔTRAF6), TRAF2 and TRAF3 (CD40ΔTRAF2/3), or both (CD40ΔTRAFs) into B cells of CD40-/- mice. The in vivo isotype switch defect in CD40-/- mice was fully corrected by WT and CD40ΔTRAF6, partially by CD40ΔTRAF2/3, and not at all by CD40ΔTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFκB in B cells were normal in WT and CD40ΔTRAF6 mice, severely impaired in CD40ΔTRAF2/3, and absent in CD40ΔTRAFs mice. These results suggest that binding to TRAF2 and/or TRAF3 but not TRAF6 is essential for CD40 isotype switching and activation in B cells.

Original languageEnglish (US)
Pages (from-to)265-276
Number of pages12
JournalImmunity
Volume17
Issue number3
DOIs
StatePublished - Sep 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Jabara, H. H., Laouini, D., Tsitsikov, E., Mizoguchi, E., Bhan, A. K., Castigli, E., Dedeoglu, F., Pivniouk, V., Brodeur, S. R., & Geha, R. S. (2002). The Binding Site for TRAF2 and TRAF3 but Not for TRAF6 Is Essential for CD40-Mediated Immunoglobulin Class Switching. Immunity, 17(3), 265-276. https://doi.org/10.1016/S1074-7613(02)00394-1