B-cell-specific ablation of β-1,4-galactosyltransferase 1 prevents aging-related IgG glycans changes and improves aging phenotype in mice

Abstract

IgG N-glycans levels change with advancing age, making it a potential biomarker of aging. β-1,4-galactosyltransferase (B4GALT) gene expression levels also increase with aging. Ultra performance liquid chromatography (UPLC) was used to examine changes inserum IgG N-glycans at six time points during the aging process. Most serum IgG N-glycans changed with aging in WT but not in CD19-cre B4GALT1 floxed mice. The relative abundance of fucosylated biantennary glycans with or without Neu5Gc structures changed with aging in heterozygous B4GALT1 floxed mice but not in homozygous B4GALT1 floxed mice. Additionally, the aging phenotype was more apparent in WT mice than in B4GALT1 floxed mice. These results demonstrate that fucosylated biantennary glycans and fucosylated biantennary glycans containing N-glycolylneuraminic acid (Neu5Gc)-linked N-acetyllactosamine (LacNAc) were highly associated with aging and were affected by the B4GALT1 floxed mouse genotype. The changing levels of fucosylated monoantennary glycans observed with aging in WT mice was reversed in B4GALT1 floxed mice and was not sex specific. In summary, B-cell-specific ablation of B4GALT1 from a glycoproteomic perspective prevented age-related changes in IgG N-glycans in mice. SignificanceIn this study, serum IgG glycoproteomic data in wild-type (WT) and B-cell-specific ablation of β-1,4-galactosyltransferase 1 mice (B4GALT) were analyzed. Results showed that fucosylated biantennary glycans with or without N-glycolylneuraminic acid (Neu5Gc)-linked N-acetyllactosamine (LacNAc) were highly associated with aging and were also affected by the B4GALT1 floxed mouse genotype. In terms of gender-specific information, the trend towards elevated fucosylated monoantennary glycans in WT mice was not seen in CD19-cre B4GALT1 floxed mice in either sex. B-cell-specific ablation of B4GALT1 plays an important role in age-related glycan changes; its specific functions and mechanisms are worthy of in-depth study. Our data suggest that investigating the relationship between galactosylation and aging may help advance the field of glycoproteomics and aging research.