Cutting Edge: A Hypomorphic Mutation in Igβ (CD79b) in a Patient with Immunodeficiency and a Leaky Defect in B Cell Development

• Published in: Journal of Immunology 2007-08, Vol.179 (4), p.2055-2059
• Main Authors: Dobbs, A. Kerry, Yang, Tianyu, Farmer, Dana, Kager, Leo, Parolini, Ornella, Conley, Mary Ellen
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.4.2055

Although null mutations in Igα have been identified in patients with defects in B cell development, no mutations in Igβ have been reported. We recently identified a patient with a homozygous amino acid substitution in Igβ, a glycine to serine at codon 137, adjacent to the cysteine required for the disulfide bond between Igα and Igβ. This patient has a small percentage of surface IgMdim B cells in the peripheral circulation (0.08% compared with 5–20% in healthy controls). Using expression vectors in 293T cells or Jurkat T cells, we show that the mutant Igβ can form disulfide-linked complexes and bring the μ 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 Igα/Igβ complex to bring the BCR to the cell surface have profound effects on B cell development.