Mutations of the Igbeta gene cause agammaglobulinemia in man.
J Exp Med
; 204(9): 2047-51, 2007 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-17709424
ABSTRACT
Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, mu heavy chain, surrogate light chain, Igalpha, and B cell linker have been found in 85-90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igbeta, which is a transmembrane protein that associates with Igalpha as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igbeta is no longer able to associate with Igalpha, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igbeta for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igbeta can cause agammaglobulinemia in man.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Agamaglobulinemia
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Antígenos CD79
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Mutação
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Itália