Divergent Golgi trafficking limits B cell-mediated IgG sialylation

Area of Science:

• Immunology
• Glycobiology
• Cell Biology

Background:

• α2,6-linked sialylation on IgG glycans impacts inflammatory conditions and IgG's anti-inflammatory function.
• Previous studies showed B cell ST6Gal1 (β-galactoside α2,6-sialyltransferase 1) ablation affected cell surface sialylation but not IgG sialylation in vivo, suggesting distinct glycosylation pathways.

Purpose of the Study:

• To investigate the distinct glycosylation and trafficking pathways of IgG and cell surface glycoproteins in B cells.
• To elucidate the roles of ST6Gal1 and Fut8 (α1,6-fucosyltransferase 8) in IgG and cell surface glycoprotein modification.

Main Methods:

• Utilized B cell hybridomas and ex vivo murine B cells.
• Employed flow cytometry and confocal microscopy.
• Analyzed IgG sialylation and fucosylation in cell culture, ex vivo, and plasma.

Main Results:

• IgG showed poor ST6Gal1-mediated sialylation and high Fut8-mediated core fucosylation in culture, contrasting with cell surface glycoproteins.
• Ex vivo B cell-produced IgG had lower sialylation than plasma-derived IgG, indicating post-release modification.
• IgG localized to fucosylation-rich regions and avoided ST6Gal1-rich compartments, supporting divergent trafficking.

Conclusions:

• IgG follows a unique trafficking pathway, prioritizing Fut8-mediated fucosylation and limiting ST6Gal1 exposure, explaining why B cell ST6Gal1 is dispensable for in vivo IgG sialylation.
• These findings reveal a mechanism for differential glycosylation of secreted versus cell surface proteins.