Establishment of fetomaternal tolerance through glycan-mediated B cell suppression
| Autor: | Rizzuto, G, Brooks, JF, Tuomivaara, ST, McIntyre, TI, Ma, S, Rideaux, D, Zikherman, J, Fisher, SJ, Erlebacher, A |
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| Rok vydání: | 2022 |
| Předmět: |
Pediatric
B-Lymphocytes General Science & Technology Placenta Contraception/Reproduction 1.1 Normal biological development and functioning Inflammatory and immune system Autoimmune Disease Trophoblasts Autoimmune Diseases Mice Good Health and Well Being Polysaccharides Pregnancy Underpinning research Immune Tolerance Animals 2.1 Biological and endogenous factors Female Antigens Aetiology |
| Zdroj: | Nature, vol 603, iss 7901 |
| Popis: | 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 Bcell tolerance to trophoblast antigens have not been identified. Here we provide evidence that glycan-mediated Bcell 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 antigens to 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 complicationsand 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. |
| Databáze: | OpenAIRE |
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