Advances in X-linked immunodeficiency diseases.
The molecular basis for three well-defined X-linked diseases has recently been identified. In X-linked agammaglobulinemia, the gene encoding a novel cytoplasmic tyrosine kinase (btk) expressed by B cells is defective. This B-cell-specific kinase belongs to a new subfamily of tyrosine kinases. The molecular defect in X-linked hyper IgM affects the gene encoding the CD40 ligand (CD40L, gp39) on T cells. This protein binds to its natural receptor, CD40, expressed constitutively by B cells. The ligand-receptor interaction initiates B-cell proliferation and isotype switching. The molecular defect in X-linked severe combined immunodeficiency disease has been assigned to the gene encoding the gamma chain of the interleukin-2 receptor (IL-2R gamma), which is constitutively expressed by T cells and is involved in the formation of high and intermediate affinity IL-2R complexes. IL-2R-gamma is responsible for the failure of X-linked severe combined immunodeficiency disease T and B lymphocytes to respond to IL-2-dependent signals.
Ochs
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HD
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Aruffo
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D000328:Adult; D000361:Agammaglobulinemia / Q000235:genetics; D023201:CD40 Ligand; D002648:Child; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D015375:Receptors, Interleukin-2 / Q000172:deficiency; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D014960:X Chromosome
D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand; D011505:Protein-Tyrosine Kinases