CD40: CD40L interactions in X-linked and non-X-linked hyper-IgM syndromes

A. Bhushan, L. R. Covey

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations


Hyper-IgM (HIM) syndrome is a rare immunodeficiency characterized by low or absent IgG, IgA, and IgE with normal or elevated levels of IgM. This disorder can be acquired or familial with either X-linked or autosomal patterns of inheritance. The X-linked form of the disease is a consequence of mutations in the CD40 ligand (CD40L) gene that encodes a protein expressed primarily on activated CD4+ T cells. The cognate interaction between CD40L on T cells and CD40 on antigen-stimulated B cells, macrophage, and dendritic cells is critical for the development of a comprehensive immune response. The non-X-linked form of HIM syndrome is heterogeneous and appears in some cases to be a consequence of mutations in the AID gene which encodes a B cell specific protein required for class switch recombination, somatic mutation, and germinal center formation. However, mutations in other unidentified genes are clearly the basis of the disease in a subset of patients. In this article, we review the essential features of the X-linked and non-X-linked forms of HIM syndrome and discuss the critical role the CD40:CD40L receptor-ligand pair plays in the pathogenesis of these immune deficiencies.

Original languageEnglish (US)
Pages (from-to)311-324
Number of pages14
JournalImmunologic Research
Issue number3
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Immunology


  • Activation induced cytidine deaminase (AID)
  • CD40
  • CD40 ligand
  • Class switch recombination
  • Germline transcription
  • Hyper IgM syndrome


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