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J Clin Invest. 1999 Oct;104(8):1115-21.

Mutations in Igalpha (CD79a) result in a complete block in B-cell development.

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  • 1Departments of Immunology, Hematology/Oncology, and Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. yoshiyuki.minegishi@stjude.org

Abstract

Mutations in Btk, mu heavy chain, or the surrogate light chain account for 85-90% of patients with early onset hypogammaglobulinemia and absent B cells. The nature of the defect in the remaining patients is unknown. We screened 25 such patients for mutations in genes encoding components of the pre-B-cell receptor (pre-BCR) complex. A 2-year-old girl was found to have a homozygous splice defect in Igalpha, a transmembrane protein that forms part of the Igalpha/Igbeta signal-transduction module of the pre-BCR. Studies in mice suggest that the Igbeta component of the pre-BCR influences V-DJ rearrangement before cell-surface expression of mu heavy chain. To determine whether Igalpha plays a similar role, we compared B-cell development in an Igalpha-deficient patient with that seen in a mu heavy chain-deficient patient. By immunofluorescence, both patients had a complete block in B-cell development at the pro-B to pre-B transition; both patients also had an equivalent number and diversity of rearranged V-DJ sequences. These results indicate that mutations in Igalpha can be a cause of agammaglobulinemia. Furthermore, they suggest that Igalpha does not play a critical role in B-cell development until it is expressed, along with mu heavy chain, as part of the pre-BCR.

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PMID:
10525050
PMCID:
PMC408581
DOI:
10.1172/JCI7696
[PubMed - indexed for MEDLINE]
Free PMC Article
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