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

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Abstract

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.

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  1. Rutgers, the State University of New Jersey, 604 Allison Road, 08854, Piscataway, NJ

    Amessha Bhushan &  Lori R. Covey

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  1. Amessha Bhushan
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  2. Lori R. Covey
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Correspondence to Lori R. Covey.

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Bhushan, A., Covey, L.R. CD40: CD40L interactions in X-linked and non-X-linked hyper-IgM syndromes. Immunol Res 24, 311–324 (2001). https://doi.org/10.1385/IR:24:3:311

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