Human plasma IgG1 repertoires are simple, unique, and dynamic
peer-reviewed · Cell Systems · 2021
| Date | 2021-12-01 |
| Type | peer-reviewed |
| Venue | Cell Systems |
| Publisher | Elsevier BV |
| Contribution | downstream-application |
| DOI | 10.1016/j.cels.2021.08.008 |
| Citations (OpenAlex) | 97 |
| Venue 2-year citedness | 5.74 |
Abstract
Although humans can produce billions of IgG1 variants through recombination and hypermutation, the diversity of IgG1 clones circulating in human blood plasma has largely eluded direct characterization. Here, we combined several mass-spectrometry-based approaches to reveal that the circulating IgG1 repertoire in human plasma is dominated by a limited number of clones in healthy donors and septic patients. We observe that each individual donor exhibits a unique serological IgG1 repertoire, which remains stable over time but can adapt rapidly to changes in physiology. We introduce an integrative protein- and peptide-centric approach to obtain and validate a full sequence of an individual plasma IgG1 clone de novo. This IgG1 clone emerged at the onset of a septic episode and exhibited a high mutation rate (13%) compared with the closest matching germline DNA sequence, highlighting the importance of de novo sequencing at the protein level. A record of this paper’s transparent peer review process is included in the supplemental information.
Methods and tools
- Human plasma IgG1 repertoire profiling: De novo MS workflow (LC-MS coupled with Stitch / native MS) for profiling the circulating human plasma IgG1 antibody repertoire, demonstrating individual-specific dynamics: landmark application of de novo to clinical antibodyomics.