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* Medical Microbiology, Department of Laboratory Medicine, University Hospital Malmö, Lund University, Malmö, Sweden;
Section of Clinical and Experimental Infectious Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden;
Section of Microbiology, Immunology, and Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden; and
Department of Otorhinolaryngology, Karolinska Institutet, Huddinge, Sweden
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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1 This work was supported by grants from Alfred Österlund, Anna and Edwin Berger, Crafoord, Greta and Johan Kock and, Marianne and Marcus Wallenberg Foundations; Swedish Medical Research Council; Swedish Society of Medicine; and Cancer Foundation at the University Hospital (Malmö, Sweden).
2 Address correspondence and reprint requests to Dr. Kristian Riesbeck, Medical Microbiology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden. E-mail address: kristian.riesbeck{at}med.lu.se
3 Abbreviations used in this paper: PRR, pathogen recognition receptor; DAPI, 4',6'-diamidino-2-phenylindole; MID, Moraxella IgD-binding protein; ODN, oligonucleotide; pAb, polyclonal Ab; PAMP, pathogen-associated molecular pattern; SpA, superantigen protein A; TEM, transmission electron microscopy; TIR, Toll/IL-1R; Usp, ubiquitous surface protein; wt, wild type.
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