IMMUNOLOGY2024™ Conference Recordings-Glycan regulation of fetomaternal tolerance

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Video Summary

The symposium introduction framed pregnancy immunology as a two-way dialogue between reproduction and host defense, with implications for neonatal and long-term health. The speaker emphasized that maternal antibodies can protect the fetus, while immune dysregulation during pregnancy can contribute to complications like preterm birth and altered infection risk.<br /><br />The main talk focused on fetal-maternal tolerance: how the fetus and placenta avoid maternal immune rejection. Using a mouse model expressing ovalbumin (OVA) on trophoblasts, the lab showed that placental antigen is released into maternal blood and lymph nodes, where it is seen by both CD8 and CD4 T cells and by antigen-specific B cells. However, trophoblast-derived antigen does not trigger normal immune activation. Instead, it causes proliferation without effector differentiation, and in some settings suppresses responses to other antigens.<br /><br />A key finding was that trophoblast OVA is heavily glycosylated and sialylated. These glycans appear to engage inhibitory receptors on B cells, especially CD22 and likely Siglec-G, dampening B-cell activation. Because B cells present trophoblast antigen to CD4 T cells, this suppression also limits T-cell responses. In contrast, non-trophoblast OVA is less sialylated and remains immunogenic. The speaker proposed that trophoblast glycosylation is a mechanism for antigen-specific tolerance during pregnancy, potentially relevant to preeclampsia, preterm birth, autoimmunity, and transplantation.

Keywords

pregnancy immunology

fetal-maternal tolerance

maternal antibodies

preterm birth

trophoblast glycosylation

B-cell inhibition

CD22 Siglec-G