The binding site for TRAF2 and TRAF3 but not for TRAF6 is essential for CD40-mediated immunoglobulin class switching

Immunity. 2002 Sep;17(3):265-76. doi: 10.1016/s1074-7613(02)00394-1.


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 (CD40deltaTRAF6), TRAF2 and TRAF3 (CD40deltaTRAF2/3), or both (CD40deltaTRAFs) into B cells of CD40(-/-) mice. The in vivo isotype switch defect in CD40(-/-) mice was fully corrected by WT and CD40deltaTRAF6, partially by CD40deltaTRAF2/3, and not at all by CD40deltaTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFkappaB in B cells were normal in WT and CD40deltaTRAF6 mice, severely impaired in CD40deltaTRAF2/3, and absent in CD40deltaTRAFs 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • B-Lymphocytes / immunology
  • CD40 Antigens / chemistry*
  • CD40 Antigens / genetics
  • CD40 Antigens / physiology
  • Genetic Complementation Test
  • Germinal Center / immunology
  • Hemocyanins / immunology
  • Immunoglobulin Class Switching / physiology*
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / blood
  • Lymphocyte Activation
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • NF-kappa B / physiology
  • Protein Binding
  • Protein Interaction Mapping
  • Proteins / physiology*
  • Recombinant Fusion Proteins / physiology
  • Sequence Deletion
  • Structure-Activity Relationship
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 3
  • Up-Regulation


  • Antigens, CD
  • CD40 Antigens
  • Immunoglobulins
  • NF-kappa B
  • Proteins
  • Recombinant Fusion Proteins
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 3
  • Hemocyanins
  • keyhole-limpet hemocyanin