Cutting edge: a hypomorphic mutation in Igbeta (CD79b) in a patient with immunodeficiency and a leaky defect in B cell development.
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.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
A Kerry
AK
Dobbs
Tianyu
T
Yang
Dana
D
Farmer
Leo
L
Kager
Ornella
O
Parolini
Mary Ellen
ME
Conley
D019943:Amino Acid Substitution / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D051925:CD79 Antigens / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D004220:Disulfides / Q000276:immunology; D015870:Gene Expression; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D020125:Mutation, Missense / Q000276:immunology
D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; D004220:Disulfides; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; C038767:immunoglobulin B