Human plasma IgG1 repertoires are simple, unique, and dynamic

Area of Science:

• Immunology
• Proteomics
• Biochemistry

Background:

• The diversity of immunoglobulin G1 (IgG1) clones in human plasma is vast but poorly characterized.
• Understanding the IgG1 repertoire is crucial for diagnosing and treating various physiological conditions.

Purpose of the Study:

• To characterize the circulating IgG1 repertoire in human plasma.
• To investigate the stability and adaptability of individual IgG1 repertoires.
• To develop a novel method for de novo sequencing of IgG1 clones.

Main Methods:

• Utilized multiple mass-spectrometry-based techniques for comprehensive analysis.
• Developed an integrative protein- and peptide-centric approach for IgG1 clone sequencing.
• Analyzed IgG1 repertoires in healthy donors and septic patients.

Main Results:

• The circulating IgG1 repertoire is dominated by a limited number of clones in both healthy and septic individuals.
• Each individual possesses a unique IgG1 repertoire that is stable over time but adaptable to physiological changes.
• A novel IgG1 clone identified during a septic episode showed a high mutation rate (13%) compared to germline DNA.

Conclusions:

• The human plasma IgG1 repertoire is surprisingly restricted, challenging previous assumptions of vast diversity.
• Individual IgG1 repertoires are dynamic, reflecting physiological status and potential disease states.
• De novo protein-level sequencing is essential for accurately characterizing novel IgG1 clones and their evolutionary history.