Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF

Immunity. 2004 Apr;20(4):441-53. doi: 10.1016/s1074-7613(04)00079-2.


Peripheral autoantigen binding B cells are poorly competitive with naive B cells for survival and undergo rapid cell death. However, in monoclonal Ig-transgenic mice lacking competitor B cells, autoantigen binding B cells can survive for extended periods. The basis for competitive elimination of autoantigen binding B cells has been unknown. Here we demonstrate that autoantigen binding B cells have increased dependence on BAFF for survival. In monoclonal Ig-transgenic mice, each autoantigen binding B cell receives elevated amounts of BAFF, exhibiting increased levels of NFkappaB p52 and of the prosurvival kinase Pim2. When placed in a diverse B cell compartment, BAFF receptor engagement and signaling are reduced and the autoantigen binding cells are unable to protect themselves from Bim and possibly other death-promoting factors induced by chronic BCR signaling. These findings indicate that under conditions where BAFF levels are elevated, autoantigen-engaged cells will be rescued from rapid competitive elimination, predisposing to the development of autoimmune disease.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoantigens / immunology*
  • Autoimmunity / physiology*
  • B-Cell Activating Factor
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immune Tolerance*
  • Immunohistochemistry
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / immunology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Autoantigens
  • B-Cell Activating Factor
  • Membrane Proteins
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor-alpha