Mutations in Igα (CD79a) result in a complete block in B-cell development
| Autor: | Dario Campana, Lisa Rapalus, Mary Ellen Conley, Fügen Ersoy, Elaine Coustan-Smith, Yoshiyuki Minegishi |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Receptors
Antigen B-Cell Biology Immunoglobulin light chain medicine.disease_cause Article Mice Agammaglobulinemia Antigens CD hemic and lymphatic diseases medicine Animals Humans Bruton's tyrosine kinase Gene B cell Genetics B-Lymphocytes Mutation Immunoglobulin mu-Chains Reverse Transcriptase Polymerase Chain Reaction General Medicine Hematopoietic Stem Cells CD79A Molecular biology Phenotype Transmembrane protein medicine.anatomical_structure Child Preschool Commentary biology.protein Female CD79 Antigens |
| Zdroj: | Journal of Clinical Investigation. 104:1115-1121 |
| ISSN: | 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|