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

Jendholm, Johan LU ; Mörgelin, Matthias LU ; Perez Vidakovics, Laura LU ; Carlsson, Michael LU ; Leffler, Hakon LU ; Cardell, Lars-Olaf LU and Riesbeck, Kristian LU (2009) In Journal of immunology (Baltimore, Md. : 1950) 182(8). p.4713-4720
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... (More)
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. (Less)
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organization
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published
subject
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
in
Journal of immunology (Baltimore, Md. : 1950)
volume
182
issue
8
pages
4713 - 4720
publisher
American Association of Immunologists
external identifiers
  • WOS:000265004700030
  • PMID:19342647
  • Scopus:65249145364
ISSN
1550-6606
DOI
10.4049/jimmunol.0803032
language
English
LU publication?
yes
id
c4b4f841-4b47-44cd-91f0-61b4730b9fb5 (old id 1392489)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19342647?dopt=Abstract
date added to LUP
2009-05-04 15:27:34
date last changed
2017-01-01 07:53:03
@article{c4b4f841-4b47-44cd-91f0-61b4730b9fb5,
  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.},
  author       = {Jendholm, Johan and Mörgelin, Matthias and Perez Vidakovics, Laura and Carlsson, Michael and Leffler, Hakon and Cardell, Lars-Olaf and Riesbeck, Kristian},
  issn         = {1550-6606},
  keyword      = {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},
  language     = {eng},
  number       = {8},
  pages        = {4713--4720},
  publisher    = {American Association of Immunologists},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Superantigen- and TLR-dependent activation of tonsillar B cells after receptor-mediated endocytosis.},
  url          = {http://dx.doi.org/10.4049/jimmunol.0803032},
  volume       = {182},
  year         = {2009},
}