Widespread Fab-arm exchange affects all endogenous serum IgG4
Nature Communications, vol. 17, pp. 410
Abstract
Out of all human antibodies, IgG4 stands out by its ability to dissociate in half-molecules and reassemble forming novel bivalent antibodies. Although this so-called Fab-arm exchange mechanism is acknowledged, detailed analysis of whether all IgG4 clones in serum are involved in such processes is not known. Here, by introducing a liquid chromatography-mass spectrometry-based approach enabling the analysis of serum IgG4 clonal repertoires, we show that widespread Fab-arm exchange occurs in serum of healthy donors and leads to a massive explosion in the molecular diversity of the IgG4 clonal repertoire. These findings provide new insight into IgG4, which plays a critical role in allergy, autoimmunity and vaccination settings, and may also impact the use of IgG4 as scaffold for therapeutics. Among the antibody subclasses, IgG4 is unique in its capability to fragment-antigen-binding (Fab)-arm exchange, a process that renders IgG4 bispecific for antigen binding. Here authors analyse serum IgG4 clonal repertoires of healthy human donors to show that Fab-arm exchange is widespread and affects all IgG4 clones.
Authors 5
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Utrecht University · Netherlands Proteomics Centre
Affiliation as printed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, CH, Utrecht, The Netherlands
Netherlands Proteomics Center, CH, Utrecht, The Netherlands
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Utrecht University · Netherlands Proteomics Centre
Affiliation as printed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, CH, Utrecht, The Netherlands
Netherlands Proteomics Center, CH, Utrecht, The Netherlands
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Utrecht University · Sanquin · Netherlands Proteomics Centre
Affiliation as printed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, CH, Utrecht, The Netherlands
Immunoglobulin Research Laboratory, Sanquin Research, CX, Amsterdam, The Netherlands
Netherlands Proteomics Center, CH, Utrecht, The Netherlands
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Maartje G. M. Huijbers Aachen Department of Human Genetics Department of Neurology, Leiden University Medical Center (LUMC)
Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Center, ZA, Leiden, The Netherlands
Department of Neurology, Leiden University Medical Center, ZA, Leiden, The Netherlands
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Albert J. R. Heck corresponding
Utrecht University · Netherlands Proteomics Centre
Affiliation as printed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, CH, Utrecht, The Netherlands. a.j.r.heck@uu.nl
Netherlands Proteomics Center, CH, Utrecht, The Netherlands. a.j.r.heck@uu.nl
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, CH, Utrecht, The Netherlands
Netherlands Proteomics Center, CH, Utrecht, The Netherlands
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