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- W4313404806 abstract "Abstract Maturation of the antibody response is critical for the generation of virus and bacteria neutralizing antibodies. It entails CSR and SHM together with plasma cell and memory B cell differentiation, and it is generally dependent on T cell help. Prompted by our finding that CSR and plasma cell differentiation can be induced in vitro by a TLR ligand together with BCR crosslinking, we hypothesized that TLR-BCR coengagement can induce a fully mature antibody response in vivo in the absence of T cells, and such coengagement must entail physical linkage of TLR and BCR ligands. To test this hypothesis, we vaccinated Tcrβ−/−Tcrδ−/− mice with NP-LPS or Salmonella Typhimurium flagellin (coengaging B-cell TLR4 with NP-specific BCR or TLR5 with flagellin-specific BCR). Vaccination of Tcrβ−/−Tcrδ−/− mice with NP-LPS or flagellin induced activation of the B cell NF-κB pathway to elicit NP or flagellin-specific class-switched IgG and IgA antibodies and plasma cells. It also induced formation of germinal center-like (GC) structures, B cell SHM, selective clonal expansion and intraclonal diversification, and generation of memory B cells. Similar antibody responses to NP and flagellin were reproduced in NSG/B mice (by grafting immunodeficient NSG mice with purified C57BL/6 mouse B cells), thereby showing that such responses could be generated in the absence of not only T cells but all other immune cells. Finally, LPS and flagellin induced class-switched and specific antibodies which neutralized E. coli and S. Typhimurium, respectively, and protected mice from lethal infection. Thus, TLR-BCR coengagement can induce a mature and protective antibody response, complete with CSR/SHM, plasma cell and memory B cell differentiation in the absence of T cells. Supported by NIH grants AI 079705, AI 105813/105813S1, AI138944, AI 167416 and Lupus Research Alliance grant LRA 641363 to Paolo Casali" @default.
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- W4313404806 date "2022-05-01" @default.
- W4313404806 modified "2023-10-16" @default.
- W4313404806 title "Intrinsic B cell TLR-BCR linked coengagement induces mature and protective antibody responses in the absence of T cells" @default.
- W4313404806 doi "https://doi.org/10.4049/jimmunol.208.supp.53.07" @default.
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