Widespread Fab-arm exchange affects all endogenous serum IgG4.

Area of Science:

• Immunology
• Biochemistry
• Mass Spectrometry

Background:

• Immunoglobulin G4 (IgG4) antibodies possess a unique Fab-arm exchange mechanism.
• The extent to which all IgG4 clones participate in this exchange in vivo remains unclear.

Purpose of the Study:

• To investigate the prevalence and impact of Fab-arm exchange on the IgG4 clonal repertoire in human serum.
• To analyze serum IgG4 repertoires using a novel LC-MS approach.

Main Methods:

• Development of a liquid chromatography-mass spectrometry (LC-MS) based method.
• Analysis of serum IgG4 clonal repertoires in healthy donors.

Main Results:

• Demonstrated widespread Fab-arm exchange of IgG4 in healthy individuals.
• Showed that Fab-arm exchange massively increases the molecular diversity of the IgG4 repertoire.
• Identified a significant expansion of the IgG4 clonal repertoire due to this mechanism.

Conclusions:

• Fab-arm exchange is a common and significant process shaping the IgG4 repertoire in healthy individuals.
• Findings offer new insights into IgG4 function in allergy, autoimmunity, and vaccination.
• The study may influence the application of IgG4 as a therapeutic scaffold.