Nov 30, 2011

Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation

Proceedings of the National Academy of Sciences of the United States of America
Jacob GlanvilleJaume Pons


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.

Mentioned in this Paper

Autoimmune Diseases
Inheritance Patterns
Twin Sibling
Eye Infections, Viral
Framework Region, Immunoglobulin
V(D)J Recombination
Lymphocyte Depletion
Variation (Genetics)

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