Mutations of the Igbeta gene cause agammaglobulinemia in man.
Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, mu heavy chain, surrogate light chain, Igalpha, and B cell linker have been found in 85-90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igbeta, which is a transmembrane protein that associates with Igalpha as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igbeta is no longer able to associate with Igalpha, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igbeta for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igbeta can cause agammaglobulinemia in man.
Ferrari
Simona
S
Medical Genetics Unit, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy. simona.ferrari@med.unibo.it
Lougaris
Vassilios
V
Caraffi
Stefano
S
Zuntini
Roberta
R
Yang
Jianying
J
Soresina
Annarosa
A
Meini
Antonella
A
Cazzola
Giantonio
G
Rossi
Cesare
C
Reth
Michael
M
Plebani
Alessandro
A
D000361:Agammaglobulinemia / Q000235:genetics*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001483:Base Sequence; D051925:CD79 Antigens / Q000235:genetics*; D004252:DNA Mutational Analysis; D004331:Drosophila melanogaster; D005455:Fluorescent Antibody Technique; D005470:Fluorometry; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D051925:CD79 Antigens; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell
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