CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance Academic Article uri icon


MeSH Major

  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • CD40 Ligand
  • HLA-D Antigens
  • Hyper-IgM Immunodeficiency Syndrome
  • Immune Tolerance
  • Immunoglobulin M


  • Hyper-IgM (HIGM) syndromes are primary immunodeficiencies characterized by defects of class switch recombination and somatic hypermutation. HIGM patients who carry mutations in the CD40-ligand (CD40L) gene expressed by CD4(+) T cells suffer from recurrent infections and often develop autoimmune disorders. To investigate the impact of CD40L-CD40 interactions on human B cell tolerance, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from three CD40L-deficient patients. Antibody characteristics and reactivity from CD40L-deficient new emigrant B cells were similar to those from healthy donors, suggesting that CD40L-CD40 interactions do not regulate central B cell tolerance. In contrast, mature naive B cells from CD40L-deficient patients expressed a high proportion of autoreactive antibodies, including antinuclear antibodies. Thus, CD40L-CD40 interactions are essential for peripheral B cell tolerance. In addition, a patient with the bare lymphocyte syndrome who could not express MHC class II molecules failed to counterselect autoreactive mature naive B cells, suggesting that peripheral B cell tolerance also depends on major histocompatibility complex (MHC) class II-T cell receptor (TCR) interactions. The decreased frequency of MHC class II-restricted CD4(+) regulatory T cells in CD40L-deficient patients suggests that these T cells may mediate peripheral B cell tolerance through CD40L-CD40 and MHC class II-TCR interactions.

publication date

  • July 9, 2007



  • Academic Article



  • eng

PubMed Central ID

  • PMC2118633

Digital Object Identifier (DOI)

  • 10.1084/jem.20062287

PubMed ID

  • 17562816

Additional Document Info

start page

  • 1583

end page

  • 93


  • 204


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