title: Analysis of the CDR3 region of the rearranged IgH chain genes in patients with severe combined immunodeficiency and severe lymphopenia.
abstract: Human B cell-negative severe combined immunodeficiency (B-SCID) is a primary immunodeficiency disease characterized by both T and B lymphocytopenia and agammaglobulinemia. Although lymphocytes of B-SCID patients express defective recombinase activity and rarely succeed in making Ag receptors, the molecular defect of the human B-SCID remains to be identified. To gain more insight into the human B-SCID defect and its effect on the Ab repertoire, we examined the Ig heavy (H) chain genes of the peripheral blood leaky B cells from three B-SCID patients. Although the number of B cells in their peripheral blood was very limited, we could obtain 41 productive VDJ recombinations from the 58 joints. The recombinations showed a grossly altered pattern characterized by short N nucleotides, short deleted nucleotides from 5' JH segments, immature JH and D segment utilization, absence of VDDJ recombination, and all but one JH segment equal to germline JH segments. Therefore, Ab repertoire of IgH chain gene in human B-SCID was limited because of restricted junctional and combinatorial diversity and few somatic mutations. Furthermore, unusually long P nucleotides were inserted in junctional sequences, which might indicate that resolution of hairpin is impaired in human B-SCID as in the murine SCID.
authors.affiliation: Department of Pediatrics, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Minegishi
authors.forename: K
authors.initials: K
authors.lastname: Akagi
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: H
authors.initials: H
authors.lastname: Okawa
authors.forename: J
authors.initials: J
authors.lastname: Yata
mesh_terms: D001402:B-Lymphocytes / Q000737:chemistry*; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007223:Infant; D008231:Lymphopenia / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016511:Severe Combined Immunodeficiency / Q000235:genetics*
chemical_list: D017931:DNA Primers; D007135:Immunoglobulin Variable Region