title: Mutations of the Igbeta gene cause agammaglobulinemia in man.
abstract: 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.
authors: Medical Genetics Unit, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy. simona.ferrari@med.unibo.it
authors: Simona
authors: S
authors: Ferrari
authors: Vassilios
authors: V
authors: Lougaris
authors: Stefano
authors: S
authors: Caraffi
authors: Roberta
authors: R
authors: Zuntini
authors: Jianying
authors: J
authors: Yang
authors: Annarosa
authors: A
authors: Soresina
authors: Antonella
authors: A
authors: Meini
authors: Giantonio
authors: G
authors: Cazzola
authors: Cesare
authors: C
authors: Rossi
authors: Michael
authors: M
authors: Reth
authors: Alessandro
authors: A
authors: Plebani
mesh_terms: 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
chemical_list: D051925:CD79 Antigens; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell
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