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
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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1392489
- author
- Jendholm, Johan
LU
; Mörgelin, Matthias
LU
; Perez Vidakovics, Laura
LU
; Carlsson, Michael
LU
; Leffler, Hakon
LU
; Cardell, Lars-Olaf
LU
and Riesbeck, Kristian
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- 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
- volume
- 182
- issue
- 8
- pages
- 4713 - 4720
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000265004700030
- pmid:19342647
- scopus:65249145364
- pmid:19342647
- 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
- 2016-04-04 09:39:55
- date last changed
- 2022-03-31 03:59:39
@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}},
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}},
language = {{eng}},
number = {{8}},
pages = {{4713--4720}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
title = {{Superantigen- and TLR-dependent activation of tonsillar B cells after receptor-mediated endocytosis.}},
url = {{http://dx.doi.org/10.4049/jimmunol.0803032}},
doi = {{10.4049/jimmunol.0803032}},
volume = {{182}},
year = {{2009}},
}