The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells

Nat Immunol. 2002 May;3(5):451-6. doi: 10.1038/ni792. Epub 2002 Apr 22.


Affinity maturation of the immune response and the generation of long-lived bone marrow (BM) plasma cells are hallmarks of CD40-dependent, thymus-dependent (TD) humoral immunity. Through disruption of the tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-binding site within the CD40 cytoplasmic domain, we selectively ablated affinity maturation and the generation of plasma cells after immunization. Mutagenesis of both the TRAF6 and TRAF2-TRAF3 sites was essential for arresting germinal center formation in response to immunization. CD40-induced B cell proliferation and early immunoglobulin production occurred even when all TRAF sites were ablated. These studies show that specific CD40-TRAF associations control well defined aspects of humoral immunity. In addition, they define the roles that TRAF-dependent and TRAF-independent pathways play in regulating antigen-driven B cell differentiation.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Base Sequence
  • CD40 Antigens / immunology*
  • CD40 Ligand / immunology
  • Cell Differentiation / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Germinal Center / immunology
  • Immunoglobulin G / analysis
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin M / analysis
  • Immunoglobulin M / biosynthesis
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Plasma Cells / cytology*
  • Plasma Cells / immunology
  • Proteins / immunology*
  • Receptors, IgE / analysis
  • Receptors, IgE / biosynthesis
  • Signal Transduction / immunology
  • TNF Receptor-Associated Factor 6


  • CD40 Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Proteins
  • Receptors, IgE
  • TNF Receptor-Associated Factor 6
  • CD40 Ligand