Frontiers in Immunology · Jul 2, 2026

Loss of ST8Sia6 mediated α-2,8-linked di-sialylation enhances T cell-dependent antibody responses and promotes autoimmunity in aged mice

By Brüchert R, Hinzpeter-Schmidt M, Röder B et al.

INTRODUCTION: Sialic acids are terminal nine-carbon sugars that form sialoglycans on the glycocalyx of all vertebrate cell surfaces. In this exposed position, they fulfill various functions in the immune system, including involvement in host-pathogen interactions and control of immune cell activation. The synthesis of sialoglycans is catalyzed by sialyltransferases. One of these is ST8Sia6, which is known to catalyze the synthesis of α-2,8-linked di-sialyl motifs and to be upregulated in plasma cells. METHODS: We studied the role of ST8Sia6 in the immune system by examining a St8sia6 knockout mouse model. RESULTS: The St8sia6-/- mice showed normal B cell and plasma cell development. However, in St8sia6-/- B cells, a stronger proliferation was induced by T cell-dependent stimuli. Additionally, an increased IgG1 response was observed upon T cell-dependent immunization. In the study, 60-week-old St8sia6-/- mice showed enlarged populations of germinal center B cells, age-induced B cells, and plasma cells. Furthermore, aged St8sia6-/- mice exhibited increased activation markers on their B cells and displayed elevated levels of anti-nuclear IgG autoantibodies, all of which are indicative of autoimmunity. We identified CD45 as a carrier protein of O-acetylated α2,8-linked di-sialic acids on plasma cells. DISCUSSION: These results demonstrate that the loss of ST8Sia6-mediated α-2,8-linked di-sialylation enhances T cell-dependent immune responses and promotes an accumulation of strongly activated B cells and an autoimmune-like phenotype upon aging.

doi.org/10.3389/fimmu.2026.1874115Open accessPubMed 42465760Mechanisms