Superantigen- and TLR-dependent activation of tonsillar B cells after receptor-mediated endocytosis.

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Abstract

Classical B lymphocyte activation is dependent on BCR cross-linking in combination with physical interaction with Th cells. Other B cell molecules that contribute to the activation are complement, cytokine, and TLRs recognizing specific pathogen-associated molecular patterns. Moraxella (Branhamella) catarrhalis is a common Gram-negative respiratory pathogen that induces proliferation in human IgD-expressing B cells independently of T cell help. The activation is initiated by the B cell superantigen Moraxella IgD-binding protein (MID) through a nonimmune cross-linking of IgD. However, IgD cross-linking alone is not sufficient to induce proliferation. In this study, we characterized the significance of TLRs in superantigen-dependent B cell activation using whole bacteria or rMID in the presence or absence of TLR ligands. IgD cross-linking by MID sensitized B cells obtained from children with tonsillar hyperplasia for mainly TLR9, whereas TLRs 1, 2, 6, and 7 were less important. The Moraxella-induced activation was inhibited when a dominant-negative TLR9 ligand was added. Interestingly, BCR-mediated endocytosis of whole Moraxella and degradation of live bacteria in naive B cells were observed with fluorescence, confocal, and transmission electron microscopy. This unique observation proved the strong intracellular TLR9 response as well as highlighted the Ag-presenting function of B cells. In conclusion, our findings suggest an important role of TLRs in the adaptive immune response and reveal novel insights into the T cell-independent B cell activation induced by bacteria.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • Palatine Tonsil: immunology, Moraxella (Branhamella) catarrhalis: immunology, Moraxella (Branhamella) catarrhalis: genetics, Lymphocyte Activation: immunology, Immunoglobulin D: immunology, Endocytosis: immunology, Bacterial: genetics, DNA, B-Lymphocytes: cytology, B-Lymphocytes: immunology, Receptors, Antigen, B-Cell: immunology, Superantigens: immunology, Toll-Like Receptors: immunology
Original languageEnglish
Pages (from-to)4713-4720
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume182
Issue number8
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes