[HTML][HTML] Mutations in Igα (CD79a) result in a complete block in B-cell development

Y Minegishi, E Coustan-Smith… - The Journal of …, 1999 - Am Soc Clin Investig
Y Minegishi, E Coustan-Smith, L Rapalus, F Ersoy, D Campana, ME Conley
The Journal of clinical investigation, 1999Am Soc Clin Investig
Mutations in Btk, μ 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 Igα, a transmembrane protein that forms part of
the Igα/Igβ signal-transduction module of the pre-BCR. Studies in mice suggest that the Igβ …
Mutations in Btk, μ 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 Igα, a transmembrane protein that forms part of the Igα/Igβ signal-transduction module of the pre-BCR. Studies in mice suggest that the Igβ component of the pre-BCR influences V-DJ rearrangement before cell-surface expression of μ heavy chain. To determine whether Igα plays a similar role, we compared B-cell development in an Igα-deficient patient with that seen in a μ 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 Igα can be a cause of agammaglobulinemia. Furthermore, they suggest that Igα does not play a critical role in B-cell development until it is expressed, along with μ heavy chain, as part of the pre-BCR.
The Journal of Clinical Investigation