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

R. Cutler Allen, Richard J. Armitage, Mary Ellen Conley, Howard Rosenblatt, Nancy A. Jenkins, Neal G. Copeland, Mary A. Bedell, Susanne Edelhoff, Christine M. Disteche, Denise K. Simoneaux, William C. Fanslow, John Belmont, Melanie K. Spriggs

Research output: Contribution to journalArticlepeer-review

789 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)990-993
Number of pages4
Issue number5097
StatePublished - 1993

ASJC Scopus subject areas

  • General


Dive into the research topics of 'CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome'. Together they form a unique fingerprint.

Cite this