| Autor: |
Boisson B, Wang YD, Bosompem A, Ma CS, Lim A, Kochetkov T, Tangye SG, Casanova JL, Conley ME |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of clinical investigation [J Clin Invest] 2013 Nov; Vol. 123 (11), pp. 4781-5. |
| DOI: |
10.1172/JCI71927 |
| Abstrakt: |
Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors. E555K in the transfected cells localized normally to the nucleus and resulted in a dominant negative effect when bound to DNA as a homodimer with wild-type E47. Mutant E47 did permit DNA binding by a tissue-specific heterodimeric DNA-binding partner, myogenic differentiation 1 (MYOD). These findings document a mutational hot-spot in E47 and represent an autosomal dominant form of agammaglobulinemia. Further, they indicate that E47 plays a critical role in enforcing the block in development of B cell precursors that lack functional antigen receptors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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