Journal
NATURE REVIEWS RHEUMATOLOGY
Volume 11, Issue 3, Pages 171-182Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrrheum.2014.220
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Funding
- NIH NHLBI Proteomics Center [N01-HV-00242]
- NIH NIAMS [R01 AR063676]
- NIH NIAID [U01 AI101981, U01 AI057229, U19 AI110491]
- NIH NCI [R33 CA183659]
- NIH NIAMS/NIAID/FNIH AMP Program UH2 AR067681 [UH2 AR067681]
- Brennan Family
- Northern California Chapter of the Arthritis Foundation (NCCAF) Center of Excellence
- Bill and Melinda Gates Foundation
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The development of high-throughput DNA sequencing technologies has enabled large-scale characterization of functional antibody repertoires, a new method of understanding protective and pathogenic immune responses. Important parameters to consider when sequencing antibody repertoires include the methodology, the B-cell population and clinical characteristics of the individuals analysed, and the bioinformatic analysis. Although focused sequencing of immunoglobulin heavy chains or complement determining regions can be utilized to monitor particular immune responses and B-cell malignancies, high-fidelity analysis of the full-length paired heavy and light chains expressed by individual B cells is critical for characterizing functional antibody repertoires. Bioinformatic identification of clonal antibody families and recombinant expression of representative members produces recombinant antibodies that can be used to identify the antigen targets of functional immune responses and to investigate the mechanisms of their protective or pathogenic functions. Integrated analysis of coexpressed functional genes provides the potential to further pinpoint the most important antibodies and clonal families generated during an immune response. Sequencing antibody repertoires is transforming our understanding of immune responses to autoimmunity, vaccination, infection and cancer. We anticipate that antibody repertoire sequencing will provide next-generation biomarkers, diagnostic tools and therapeutic antibodies for a spectrum of diseases, including rheumatic diseases.
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