title: Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation.
abstract: A diverse antibody repertoire is essential for an effective adaptive immune response to novel molecular surfaces. Although past studies have observed common patterns of V-segment use, as well as variation in V-segment use between individuals, the relative contributions to variance from genetics, disease, age, and environment have remained unclear. Using high-throughput sequence analysis of monozygotic twins, we show that variation in naive V(H) and D(H) segment use is strongly determined by an individual's germ-line genetic background. The inherited segment-use profiles are resilient to differential environmental exposure, disease processes, and chronic lymphocyte depletion therapy. Signatures of the inherited profiles were observed in class switched germ-line use of each individual. However, despite heritable segment use, the rearranged complementarity-determining region-H3 repertoires remained highly specific to the individual. As it has been previously demonstrated that certain V-segments exhibit biased representation in autoimmunity, lymphoma, and viral infection, we anticipate our findings may provide a unique mechanism for stratifying individual risk profiles in specific diseases.
authors: Protein Engineering, Rinat-Pfizer Inc, South San Francisco, CA 94080, USA.
authors: Jacob
authors: J
authors: Glanville
authors: Tracy C
authors: TC
authors: Kuo
authors: H-Christian
authors: HC
authors: von Büdingen
authors: Lin
authors: L
authors: Guey
authors: Jan
authors: J
authors: Berka
authors: Purnima D
authors: PD
authors: Sundar
authors: Gabriella
authors: G
authors: Huerta
authors: Gautam R
authors: GR
authors: Mehta
authors: Jorge R
authors: JR
authors: Oksenberg
authors: Stephen L
authors: SL
authors: Hauser
authors: David R
authors: DR
authors: Cox
authors: Arvind
authors: A
authors: Rajpal
authors: Jaume
authors: J
authors: Pons
mesh_terms: D000906:Antibodies / Q000235:genetics* / Q000276:immunology*; D014644:Genetic Variation / Q000187:drug effects; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D040582:Inheritance Patterns / Q000187:drug effects / Q000235:genetics*; D008212:Lymphocyte Depletion; D014427:Twins / Q000235:genetics; D060152:V(D)J Recombination / Q000187:drug effects / Q000235:genetics
chemical_list: D000906:Antibodies; D007135:Immunoglobulin Variable Region; D007166:Immunosuppressive Agents