Cutting edge:: A hypomorphic mutation in igβ (CD79b) in a patient with immunodeficiency and a leaky defect in BCeH development

Although null mutations in Ig alpha have been identified in patients with defects in B cell development, no mutations in)Ig beta have been reported. We recently identified a patient with a homozygous amino acidsubstitution in Ig beta, a glycine to serine at codon 137, adjacent to the cysteine required for the disulfide bond between Iga and Ig beta. This patient has a small percentage of surface JgM(dim) B cells in the peripheral circulation (0. 08 % compared with 5-20% in healthy controls). Using expression vectors in 293 T cells or Jurkat T cells, we show that the mutant Ig beta can form disulfide-linked complexes and bring the mu H chain to the cell surface as part of the BCR but is inefficient at both tasks. The results show that minor changes in the ability of the Ig alpha/Ig beta complex to bring the BCR to the cell surface have profound effects on B cell development.