Gabi’s postdoctoral work in Adrian Erlebacher’s lab at UCSF identified a checkpoint that limits harmful B cell responses to placental trophoblast antigens. Our lab investigates mechanisms of trophoblast antigen-specific maternal B cell suppression. Trophoblast antigen carries sialoglycans, which engage inhibitory B cell receptors to suppress activation. We hypothesize that sialoglycan recognition induces a reversible state of antigen-specific B cell tolerance underscored by a distinct transcriptional program. More broadly, we are exploring whether similar antigen-intrinsic mechanisms shape maternal CD4 and CD8 T cell tolerance or unresponsiveness.

We hypothesize that protective mechanisms prevent placental-specific IgG from harming pregnancy. Using the OVA model antigen system, we manipulate OVA-specific cells and antibodies to assess IgG pathogenicity when targeting trophoblasts versus other cell types. One hypothesis is that anti-placental IgG undergoes sialylation during pregnancy, reducing effector function, as supported by literature on IgG glycosylation and anti-inflammatory effects. We will investigate whether anti-placental IgG glycosylation and effector functions change during pregnancy and test if sialylation is required for suppressing pathogenicity. Alternatively, we will explore whether placentas possess unique resistance to harmful antibodies using in vivo, in vitro, and genomic approaches.

Beyond their immunosuppressive roles, trophoblasts are highly proliferative, invasive, and angiogenic — traits essential for fetal development but also linked to gestational trophoblastic neoplasms (GTN), cancers arising from malignant trophoblast transformation. These “foreign” tumor cells resist immune elimination, challenging principles of cancer immunology. We aim to uncover immune evasion strategies in these rare tumors, with implications for both GTN treatment and broader cancer immunology. Our hypothesis is that glycan-dependent immune evasion used by trophoblasts during pregnancy is coopted by GTN to suppress anti-tumor immunity. Using a novel mouse choriocarcinoma model, we are defining its immune escape mechanisms and collaborating with MSK oncologists, Dr. Ying Liu and Dr. Aaron Praiss, for high-dimensional profiling of human GTN specimens.

Pregnancy is not a state of generalized immunosuppression, but immune responses to non-conceptus antigens are clearly modulated. We have stumbled upon differences in immune responses between pregnant and virgin mice. Notably, maternal follicular helper T cell (Tfh cell) responses to vaccination were reduced in pregnancy, yet germinal center B cell and antibody responses, including affinity maturation, remained intact. This raises fundamental questions about germinal center biology during pregnancy, particularly what signals support B cell responses. We are investigating B cell, antibody, and Tfh cell responses to vaccination and infection throughout pregnancy. More broadly, we propose that immune modulation during pregnancy helps constrain conceptus-specific responses, linking our studies of both tolerance and immunity.