Divergent Golgi trafficking limits B cell-mediated IgG sialylation.

The degree of α2,6-linked sialylation on IgG glycans is associated with a variety of inflammatory conditions and is thought to drive IgG anti-inflammatory activity. Previous findings revealed that ablation of β-galactoside α2,6-sialyltransferase 1 (ST6Gal1) in B cells failed to alter IgG sialylation in vivo, yet resulted in the loss of B cell surface α2,6 sialylation, suggesting divergent pathways for IgG and cell surface glycoprotein glycosylation and trafficking. Employing both B cell hybridomas and ex vivo murine B cells, we discovered that IgG was poorly sialylated by ST6Gal1 and highly core fucosylated by α1,6-fucosyltransferase 8 (Fut8) in cell culture. In contrast, cell surface glycoproteins on IgG-producing cells showed the opposite pattern by flow cytometry, with high α2,6 sialylation and low α1,6 fucosylation. Paired studies further revealed that ex vivo B cell-produced IgG carried significantly less sialylation compared with IgG isolated from the plasma of matched animals, providing evidence that IgG sialylation increases after release in vivo. Finally, confocal analyses demonstrated that IgG poorly localized to subcellular compartments rich in sialylation and ST6Gal1, and strongly to regions rich in fucosylation and Fut8. These findings support a model in which IgG subcellular trafficking diverges from the canonical secretory pathway by promoting Fut8-mediated core fucosylation and limiting exposure to and modification by ST6Gal1, providing a mechanism for why B cell-expressed ST6Gal1 is dispensable for IgG sialylation in vivo.