TRAF2 and TRAF3 independently mediate Ig class switching driven by CD40

• Published in: International immunology 2009-04, Vol.21 (4), p.477-488
• Main Authors: Jabara, Haifa H., Weng, Yu, Sannikova, Tatyana, Geha, Raif S.
• Format: Article
• Language: English
• Subjects: Animals; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; CD40 Antigens - genetics; CD40 Antigens - immunology; CD40 Antigens - metabolism; Hemocyanins - immunology; IgE; Immunoglobulin Class Switching - immunology; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunoglobulin M - blood; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; isotype switching; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases - immunology; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - immunology; NF-kappa B - metabolism; Original Research Papers; Receptors, IgE - immunology; Receptors, IgE - metabolism; Signal Transduction - immunology; TNF Receptor-Associated Factor 2 - immunology; TNF Receptor-Associated Factor 2 - metabolism; TNF Receptor-Associated Factor 3 - immunology; TNF Receptor-Associated Factor 3 - metabolism
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxp013

The isotype switch defect in CD40−/− mice is corrected by wild-type (WT) CD40 transgene, but not by a mutant CD40 transgene that does not bind tumor necrosis factor receptor-associated factors (TRAF) 2 and 3. To define the individual roles of TRAF2 and TRAF3 in CD40 activation of B cells, we introduced mutant CD40 transgenes that selectively lack the ability to bind TRAF2 (ΔTR2), TRAF3 (ΔTR3) or both (ΔTR2,3) into B cells of CD40−/− mice. Serum IgG1 and IgE levels, IgG1 antibody response to sub-optimal doses of the T cell-dependent antigen keyhole limpet hemocyanin, germinal center formation, CD40-mediated proliferation, isotype switching and activation of the non-canonical NF-κB pathway were partially diminished in ΔTR2 and ΔTR3 mice and virtually absent in ΔTR2,3 mice. These results suggest that TRAF2 and TRAF3 can each independently mediate class switch recombination (CSR) driven by CD40, but both are required for optimal CD40-driven isotype switching.