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

Summary, in English

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.

• Författare: Johan Jendholm; Matthias Mörgelin; Laura Perez Vidakovics; Michael Carlsson; Hakon Leffler; Lars-Olaf Cardell; Kristian Riesbeck
• Avdelning/ar: Klinisk mikrobiologi, Malmö; Infektionsmedicin; Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG; Clinical and Experimental Allergy Research
• Publiceringsår: 2009
• Språk: Engelska
• Sidor: 4713-4720
• Publikation/Tidskrift/Serie: Journal of immunology
• Volym: 182
• Issue: 8
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/19342647?dopt=Abstract; http://dx.doi.org/10.4049/jimmunol.0803032
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Association of Immunologists
• Ämne: Immunology in the medical area
• Nyckelord: 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
• Status: Published
• Forskningsgrupp: Clinical Microbiology, Malmö; Clinical and Experimental Allergy Research
• ISBN/ISSN/Övrigt: ISSN: 1550-6606