CD40 ligand gene defects responsible for x-linked hyper-IgM syndrome

Journal Article · Fri Feb 12 04:00:00 EST 1993 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.7679801· OSTI ID:6653308

Allen, R C; Simoneaux, D K; Belmont, J; Rosenblatt, H ^[1]; Armitage, R J; Fanslow, W C; Spriggs, M K ^[2]; Conley, M E ^[3]; Jenkins, N A; Copeland, N G; Bedell, M A ^[4]; Edelhoff, S; Disteche, C M ^[5]

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1. Baylor College of Medicine, Houston, TX (United States)
2. Immunex Research and Development Corp., Seattle, WA (United States)
3. Univ. of Tennessee, Memphis, TN (United States) St. Jude Children's Research Hospital, Memphis, TN (United States)
4. National Cancer Inst., Frederick, MD (United States)
5. Univ. of Washington, Seattle (United States)

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. DC40L 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 of 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.

• OSTI ID: 6653308
• Journal Information: Science (Washington, D.C.); (United States), Journal Name: Science (Washington, D.C.); (United States) Vol. 259:5097; ISSN SCIEAS; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CELL MEMBRANES
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DETECTION
DISEASES
GENE MUTATIONS
GLOBULINS
GLYCOPROTEINS
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
HUMAN X CHROMOSOME
IMMUNOGLOBULINS
LEUKOCYTES
LYMPHOCYTES
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
RECEPTORS
SOMATIC CELLS
X CHROMOSOME