Dataset Information

Establishment of fetomaternal tolerance via glycan-mediated B cell suppression

ABSTRACT: The immune system must be able to distinguish self from non-self. During pregnancy, the mother’s immune system does not recognize the placenta as foreign because proteins expressed by tropbholasts, the placental cells that interface with the maternal immune system, do not activate maternal T cells. These activation defects have been previously attributed to suppression by regulatory T cells, while mechanisms of maternal B cell tolerance to trophoblast antigens have not been identified. In this study, we provide evidence that glycan-mediated B cell suppression plays a key role in establishing fetomaternal tolerance in mice. We find that trophoblast antigen-specific B cells are profoundly suppressed via CD22/LYN inhibitory signaling, in turn implicating the antigens’ sialic acids as key suppressive determinants. We also find that B cells mediate the antigen’s MHCII-restricted presentation to CD4 T cells, leading to T cell suppression. The specific goal of the mass spectrometry undertaking deposited here was to identify sialylated “true” placental-derived proteins present in the human and mouse serum proteome during pregnancy. Overall, our findings reveal protein glycosylation as a fundamental feature of placental “self-recognition” and may have relevance to pregnancy complications and tumor immune evasion. Furthermore, we anticipate these findings will enhance synthetic efforts to harness glycans to control antigen-specific immune responses in the treatment of autoimmune diseases.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Blood Serum

SUBMITTER: Sami Tuomivaara

LAB HEAD: Susan J Fisher

PROVIDER: PXD029966 | Pride | 2022-01-12

REPOSITORIES: Pride

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			Action	DRS
	2021-11-10.OVA10-1.group	Other
	2021-11-10.OVA10-1__FDR.xlsx	Xlsx
	2021-11-10.OVA10-1_inj_1.mzML	Mzml
	2021-11-10.OVA10-1_inj_1.wiff	Wiff
	2021-11-10.OVA10-1_inj_1.wiff.scan	Wiff

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Establishment of fetomaternal tolerance through glycan-mediated B cell suppression.

Rizzuto G G Brooks J F JF Tuomivaara S T ST McIntyre T I TI Ma S S Rideaux D D Zikherman J J Fisher S J SJ Erlebacher A A

Nature 20220302 7901

Discrimination of self from non-self is fundamental to a wide range of immunological processes1. During pregnancy, the mother does not recognize the placenta as immunologically foreign because antigens expressed by trophoblasts, the placental cells that interface with the maternal immune system, do not activate maternal T cells2. Currently, these activation defects are thought to reflect suppression by regulatory T cells3. By contrast, mechanisms of B cell tolera ...[more]

PMID: 35236989

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