International Immunology Advance Access originally published online on February 19, 2009
International Immunology 2009 21(4):477-488; doi:10.1093/intimm/dxp013
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TRAF2 and TRAF3 independently mediate Ig class switching driven by CD40
1 Division of Immunology, Children's Hospital
2 Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Correspondence to: R. S. Geha; E-mail: raif.geha{at}childrens.harvard.edu
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 (
TR2), TRAF3 (TR3) or both (TR2,3) 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-
B pathway were partially diminished in TR2 and TR3 mice and virtually absent in TR2,3 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.
Keywords: B cells, IgE, isotype switching
Transmitting editor: C. Terhorst
Received 17 September 2008, accepted 28 January 2009.