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- W4313359655 abstract "Abstract Immune protection against viral infections relies on the generation of efficient B cell responses and neutralizing antibody (nAb) production. In order to reach full activation, B cells undergo several activation checkpoints in lymph nodes (LN) draining infections sites. In particular, crosstalk between antigen-specific B cells and T follicular helper (Tfh) cells is key to the formation of germinal centers and to the production of high affinity nAbs. However, some viruses (such as lymphocytic choriomeningitis virus [LCMV] in mice, and hepatitis B and C in humans) fail to induce early, potent nAb responses, and can establish persistent infections. We asked whether the lack of nAbs upon LCMV infection reflects a defect in T cell help to B cells. To address this question, we sought to analyze the generation and activation of Tfh cells in the context of LCMV infection as compared to VSV infection, a benchmark for effective nAb responses. Preliminary data show a striking compartmentalization of CD4 T helper responses. In particular, the vast majority of VSV-specific CD4+ T cells differentiated into Tfh and migrated to B cell follicles as early as three days after infection. By contrast, LCMV infection resulted in almost exclusive Th1 differentiation, with little or no Tfh induction. Interestingly, this was independent of the affinity of the TCR for the antigen, since the same LCMV glycoprotein antigen induced Tfh cell differentiation when expressed on a VSV backbone. We are currently utilizing intravital microscopy and gene-expression profile analyses to pinpoint the mechanisms underlying this reduced Tfh differentiation in the context of LCMV infection. Elucidating these mechanisms could pave the way to more efficient vaccination strategies." @default.
- W4313359655 created "2023-01-06" @default.
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- W4313359655 date "2018-05-01" @default.
- W4313359655 modified "2023-09-27" @default.
- W4313359655 title "Determinants of T follicular helper cell development upon viral infections" @default.
- W4313359655 doi "https://doi.org/10.4049/jimmunol.200.supp.182.1" @default.
- W4313359655 hasPublicationYear "2018" @default.
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