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

J Clin Invest. 1999 Oct;104(8):1115-21. doi: 10.1172/JCI7696.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agammaglobulinemia / etiology*
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • B-Lymphocytes / physiology*
  • CD79 Antigens
  • Child, Preschool
  • Female
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Immunoglobulin mu-Chains / physiology
  • Mice
  • Mutation*
  • Phenotype
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antigens, CD
  • CD79 Antigens
  • CD79A protein, human
  • Cd79a protein, mouse
  • Immunoglobulin mu-Chains
  • Receptors, Antigen, B-Cell