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- W4313405744 abstract "Abstract B1 cells differ from B2 cells in their developmental origin, phenotype, and function. They are anatomically located in various tissues of the immune system, and contribute to around 90% of the circulating antibodies in blood. B1 cells are often activated in a T-cell independent manner promoted by either antigens that contain a B-cell mitogen such as LPS, or by molecules that have highly repetitive structures such as bacterial capsular polysaccharides, with both pathways having the potential to undergo class-switch recombination and somatic hypermutation. Previously, we have shown that immunization with bacterial outer membrane vesicles engineered to display defined glycan structures on their surface (glycOMVs) promotes a strong glycan-specific IgG response for a wide range of bacterial and mammalian glycans. Here, we show that the structure of lipid A in these (glycOMVs) displaying the oncofetal antigen polysialic acid (polySia), influences the activation and class-switching of polySia-specific B1 cells from the spleen and peritoneal cavity in mice. We found that structural remodeling of lipid A from its normal hexa-acylated structure to a penta-acylated variant prevents the activation of polySia-specific B1 cells in the spleen and enhances the activation of polySia-specific B2 cells from the peritoneal cavity. Interestingly, we observed no changes in the glycan-specific IgG titers following immunization of wildtype B6 mice with either construct, even though there was no B cell activation in the spleen of mice receiving penta-acylated glycOMVs. However, these same glycOMVs failed to promote a glycan-specific IgG response in T-deficient mice, suggesting that this response was entirely T-cell dependent. This work was supported by Bill and Melinda Gates Foundation grant OPP1217652 (to MPD), NSF grants CBET-1159581, CBET-1264701 and CBET-1936823 (to MPD), the Defense Threat Reduction Agency (DTRA) grants HDTRA1-15-10052 and HDTRA1-20-10004 (to MPD), NIH grants 1R01GM137314 and 1R01GM127578 (to MPD) and the Fleming Scholars Fellowship (to NLB)." @default.
- W4313405744 created "2023-01-06" @default.
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- W4313405744 date "2022-05-01" @default.
- W4313405744 modified "2023-10-16" @default.
- W4313405744 title "Changes in the structure of lipid A in glycosylated outer membrane vesicles (glycOMVs) suppress the activation of glycan-specific B1 cells <i>in vivo</i>" @default.
- W4313405744 doi "https://doi.org/10.4049/jimmunol.208.supp.116.12" @default.
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