title: Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange.
abstract: Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B cells from 110 healthy adult donors. We found that DJH rearrangements and nonproductive VHDJH rearrangements share many features but differ significantly in their use of D genes and propensity for somatic hypermutation. In D to JH gene rearrangements, the D genes proximal to the JH locus are used more frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus.
authors.affiliation: Department of Clinical Biochemistry, Roskilde University Hospital, DK-5000 Odense, Denmark;
authors.forename: Tina Østergaard
authors.initials: TØ
authors.lastname: Hansen
authors.affiliation: Maersk Mc-Kinney Moller Institute, Faculty of Sciences, University of Southern Denmark, DK-5000 Odense, Denmark; and.
authors.forename: Anders Blaabjerg
authors.initials: AB
authors.lastname: Lange
authors.affiliation: Department of Clinical Immunology, Odense University Hospital, DK-5000 Odense, Denmark barington@dadlnet.dk.
authors.forename: Torben
authors.initials: T
authors.lastname: Barington
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023061:Gene Order; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D056426:Genetic Loci; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015203:Reproducibility of Results; D027041:Somatic Hypermutation, Immunoglobulin; D060152:V(D)J Recombination
chemical_list: D007143:Immunoglobulin Heavy Chains