title: Evidence for defects in V(D)J rearrangements in patients with severe combined immunodeficiency.
abstract: We investigated the patterns of DNA rearrangements at loci for Ig JH genes in patients with severe combined immunodeficiency (SCID). Four SCID patients without B cells (B- SCID) and four SCID patients with B cells (B+ SCID) were examined. Bone marrow cells of these patients were transformed with EBV. The majority of the transformed cells from three B- SCID patients had the germline configuration at their JH gene loci. The rearranged fragments from one patient were analyzed extensively. The rearranged regions in all of the fragments had a common structure wherein two fragments derived from the JH-S mu region were connected inversely. The possible presence of rearranged forms of VHDJH and DHQ52JH sequences in bone marrow cells of two B- SCID patients were examined directly by the polymerase chain reaction (PCR) method. In one patient, we found neither a VHDJH sequence nor a DHQ52JH sequence within the range of sensitivity of the PCR method. In another patient, we found a VHDJH sequence at an extremely low level and DHQ52JH sequences at a relatively low level. Either RAG-1 or RAG-2 gene was not expressed in the B- SCID-derived cell lines. B+ SCID patients did not show any abnormalities in terms of VHDJH rearrangements. These results indicate that B- SCID may be caused by defects in factors involved in V(D)J rearrangements.
authors.affiliation: Department of Pediatrics, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: I
authors.initials: I
authors.lastname: Tsuge
authors.forename: Y
authors.initials: Y
authors.lastname: Kamachi
authors.forename: S
authors.initials: S
authors.lastname: Torii
authors.forename: K
authors.initials: K
authors.lastname: Utsumi
authors.forename: Y
authors.initials: Y
authors.lastname: Akahori
authors.forename: Y
authors.initials: Y
authors.lastname: Ichihara
authors.forename: Y
authors.initials: Y
authors.lastname: Kurosawa
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D018398:Homeodomain Proteins; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; D011506:Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein