Immunologic Research

, Volume 24, Issue 3, pp 311–324

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


DOI: 10.1385/IR:24:3:311

Cite this article as:
Bhushan, A. & Covey, L.R. Immunol Res (2001) 24: 311. doi:10.1385/IR:24:3:311


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 cells 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 play in the pathogenesis of these immune deficiencies.

Key Words

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

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  1. 1.Rutgers, the State University of New JerseyPiscataway