title: Complete arrest from pro- to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations.
abstract: The B-cell lineage in a patient with B-cell-negative severe combined immunodeficiency (SCID) was analysed by using antisurrogate light chain (SL) MoAbs. Peripheral CD3(+) T cells and CD19(+) B cells were absent in the patient. The common gamma (gamma c) chain was expressed normally on the patient's peripheral NK cells and his peripheral mononuclear cells did not possess any mutations in recombinase activating gene (RAG)-1, 2. Normal levels of expression of Ku70 and Ku80 protein were found by Western blot analysis. The patient did, however, display an increase in fibroblast sensitivity to irradiation. Furthermore, flow cytometric analyses of bone marrow cells showed that surface IgM and cytoplasmic mu positive cells were absent and that CD19(+) B cells were composed of only CD34(+) terminal deoxynucleotidyl transferase (TdT)(+) SL(+) pro-B cells. The complete arrest of pro- to pre-B cell development in the SCID patient's bone marrow suggests that some genes involved in V(D)J recombination, excepting the RAG gene, may play a causative role in the immunodeficiency.
authors.affiliation: Department of Paediatrics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan. agemats@gipac.shinshu-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Agematsu
authors.forename: H
authors.initials: H
authors.lastname: Nagumo
authors.forename: S
authors.initials: S
authors.lastname: Hokibara
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Wada
authors.forename: A
authors.initials: A
authors.lastname: Yachie
authors.forename: H
authors.initials: H
authors.lastname: Kanegane
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: K
authors.initials: K
authors.lastname: Sugita
authors.forename: H
authors.initials: H
authors.lastname: Karasuyama
authors.forename: A
authors.initials: A
authors.lastname: Komiyama
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein