Interleukin-10 enhances IgG galactosylation and sialylation

IgG antibodies contain a conserved N-linked glycosylation site at Asn297 in the Fc region, and variations in Fc glycosylation critically influence antibody effector functions. While inflammatory signals during immunization are known to reduce IgG Fc galactosylation and sialylation, the counter-regulatory pathways that enhance these modifications remain poorly understood. Here, we investigated the association of the anti-inflammatory cytokine IL-10 with germinal center (GC) responses and IgG Fc glycosylation following protein immunization in mice. Blockade of IL-10 receptor signaling after immunization with a model protein and the adjuvant Alum reduced Fc galactosylation and sialylation of antigen-specific IgG1 and was associated with decreased expression of the sialyltransferase St6gal1 in antigen-specific GC B cells and plasma cells. Although IFNγ is known to suppress IgG Fc galactosylation and sialylation, Alum immunization paradoxically induced both high levels of Fc galactosylation and sialylation as well as a high frequency of IFNγ-producing CD4⁺ T follicular cells. Using IL-10 reporter mice, we resolved this apparent discrepancy by identifying a substantial population of IL-10⁺ IFNγ⁺ double-producing T follicular cells following Alum immunization. Ex vivo murine and human B cell culture experiments further showed that IL-10 counteracts IFNγ-mediated downregulation of St6gal1. Together, these findings identify an association between IL-10 signaling and increased St6gal1 expression in GC B cells and PCs, as well as increased IgG Fc galactosylation and sialylation. Furthermore, the data identify a population of IL-10⁺ IFNγ⁺ T follicular cells that may contribute to the IL-10-associated glycosylation changes. Our study supports a link between cytokine environments and IgG Fc glycosylation and provides a framework for future studies investigating how IL-10-associated pathways shape IgG glycosylation in vaccination and inflammatory disease settings.