Cutting edge: a hypomorphic mutation in Igbeta (CD79b) in a patient with immunodeficiency and a leaky defect in B cell development.

A Kerry Dobbs, Tianyu Yang, Dana Farmer, Leo Kager, Ornella Parolini, Mary Ellen Conley

Journal: Journal of immunology (Baltimore, Md. : 1950) 2007;179(4):2055-9

PMID: 17675462

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Abstract

Although null mutations in Igalpha have been identified in patients with defects in B cell development, no mutations in Igbeta have been reported. We recently identified a patient with a homozygous amino acid substitution in Igbeta, a glycine to serine at codon 137, adjacent to the cysteine required for the disulfide bond between Igalpha and Igbeta. This patient has a small percentage of surface IgM(dim) 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 Igbeta 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 Igalpha/Igbeta complex to bring the BCR to the cell surface have profound effects on B cell development.

Address: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

DOI: 10.4049/jimmunol.179.4.2055