Assessment of IgG-Fc glycosylation from individual RhD-specific B cell clones reveals regulation at clonal rather than clonotypic level.

Autor: de Graaf EL; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., Larsen MD; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., van der Bolt N; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands., Visser R; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., Verhagen OJHM; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Hipgrave Ederveen AL; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Koeleman CAM; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., van der Schoot CE; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Wuhrer M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Vidarsson G; Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2024 Mar; Vol. 171 (3), pp. 428-439. Date of Electronic Publication: 2023 Dec 14.
DOI: 10.1111/imm.13737
Abstrakt: The type and strength of effector functions mediated by immunoglobulin G (IgG) antibodies rely on the subclass and the composition of the N297 glycan. Glycosylation analysis of both bulk and antigen-specific human IgG has revealed a marked diversity of the glycosylation signatures, including highly dynamic patterns as well as long-term stability of profiles, yet information on how individual B cell clones would contribute to this diversity has hitherto been lacking. Here, we assessed whether clonally related B cells share N297 glycosylation patterns of their secreted IgG. We differentiated single antigen-specific peripheral IgG + memory B cells into antibody-secreting cells and analysed Fc glycosylation of secreted IgG. Furthermore, we sequenced the variable region of their heavy chain, which allowed the grouping of the clones into clonotypes. We found highly diverse glycosylation patterns of culture-derived IgG, which, to some degree, mimicked the glycosylation of plasma IgG. Each B cell clone secreted IgG with a mixture of different Fc glycosylation patterns. The majority of clones produced fully fucosylated IgG. B cells producing afucosylated IgG were scattered across different clonotypes. In contrast, the remaining glycosylation traits were, in general, more uniform. These results indicate IgG-Fc fucosylation to be regulated at the single-clone level, whereas the regulation of other glycosylation traits most likely occurs at a clonotypic or systemic level. The discrepancies between plasma IgG and culture-derived IgG, could be caused by the origin of the B cells analysed, clonal dominance or factors from the culture system, which need to be addressed in future studies.
(© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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