title: CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome.
abstract: The ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and immunoglobulin secretion. Abnormalities in the CD40L gene were associated with an X-linked immunodeficiency in humans [hyper-IgM (immunoglobulin M) syndrome]. This disease is characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. CD40L complementary DNAs from three of four patients with this syndrome contained distinct point mutations. Recombinant expression of two of the mutant CD40L complementary DNAs resulted in proteins incapable of binding to CD40 and unable to induce proliferation or IgE secretion from normal B cells. Activated T cells from the four affected patients failed to express wild-type CD40L, although their B cells responded normally to wild-type CD40L. Thus, these CD40L defects lead to a T cell abnormality that results in the failure of patient B cells to undergo immunoglobulin class switching.
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: R J
authors.initials: RJ
authors.lastname: Armitage
authors.forename: M E
authors.initials: ME
authors.lastname: Conley
authors.forename: H
authors.initials: H
authors.lastname: Rosenblatt
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: M A
authors.initials: MA
authors.lastname: Bedell
authors.forename: S
authors.initials: S
authors.lastname: Edelhoff
authors.forename: C M
authors.initials: CM
authors.lastname: Disteche
authors.forename: D K
authors.initials: DK
authors.lastname: Simoneaux
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D004247:DNA / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014960:X Chromosome
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D004247:DNA