CD40:CD40L interactions in X-linked and non-X-linked hyper-IgM syndromes.
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 AlD 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.
Bhushan
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Dept. of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway 08854, USA.
Covey
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics* / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D009154:Mutation; D015398:Signal Transduction; D014158:Transcription, Genetic; D014960:X Chromosome
D019013:CD40 Antigens; D007075:Immunoglobulin M; D023201:CD40 Ligand