Superantigen- and TLR-dependent activation of tonsillar B cells after receptor-mediated endocytosis
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Immunology |
Volume | 182 |
Issue number | 8 |
Pages (from-to) | 4713-20 |
Number of pages | 7 |
ISSN | 0022-1767 |
DOIs | |
Publication status | Published - 2009 |
Externally published | Yes |
Bibliographical note
Keywords: B-Lymphocytes; Child; Child, Preschool; DNA, Bacterial; Endocytosis; Female; Humans; Immunoglobulin D; Lymphocyte Activation; Male; Microscopy, Electron, Transmission; Moraxella (Branhamella) catarrhalis; Palatine Tonsil; Receptors, Antigen, B-Cell; Superantigens; Toll-Like Receptors
ID: 49745317