Establishment of fetomaternal tolerance through glycan-mediated B cell suppression

Discrimination of self from non-self is fundamental to a wide range of immunological processes(1). 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 cells(2). Currently, these activation defects are thought to reflect suppression by regulatoryTcells(3). By contrast, mechanisms of B cell tolerance to trophoblast antigens have not been identified. Here we provide evidence that glycan-mediated B cell suppression has a key role in establishing fetomaternal tolerance in mice. B cells specific for a model trophoblast antigen are strongly suppressed through CD22-LYN inhibitory signalling, which in turn implicates the sialylated glycans of the antigen as key suppressive determinants. Moreover, B cells mediate the MHC-class-II-restricted presentation of antigensto CD4(+) T cells, which leads to T cell suppression, and trophoblast-derived sialoglycoproteins are released into the maternal circulation during pregnancy in mice and humans. How protein glycosylation promotes non-immunogenic placental self-recognition may have relevance to immune-mediated pregnancy complications and to tumour immune evasion. We also anticipate that our findings will bolster efforts to harness glycan biology to control antigen-specific immune responses in autoimmune disease.

Automated summary

The recognition and tolerance of the placenta by the maternal immune system is crucial for a healthy pregnancy. This study provides evidence that glycan-mediated B cell suppression plays a key role in establishing fetomaternal tolerance in mice. The release of trophoblast-derived sialoglycoproteins into the maternal circulation during pregnancy suggests potential implications for immune-mediated pregnancy complications and tumor immune evasion.