Tomasz Piotr Wypych1, Roberta Marzi2, Gregory F Wu3, Antonio Lanzavecchia4, Federica Sallusto5. 1. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address: tomasz.wypych@chuv.ch. 2. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. 3. Department of Neurology, Washington University, St Louis, Mo. 4. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland; Institute of Microbiology, ETH Zürich, Zurich, Switzerland. 5. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. Electronic address: federica.sallusto@irb.usi.ch.
Abstract
BACKGROUND: The importance of B lymphocytes to present antigens for antibody production is well documented. In contrast, very little is known about their capacity to influence CD4+ T-cell activation during a primary or secondary response to allergens. OBJECTIVE: Using mouse models of asthma, we investigated the role of B cells as antigen-presenting cells in priming and maintenance of TH cell responses. METHODS: Mice were immunized through the intranasal route with house dust mite (HDM) extract derived from Dermatophagoides pteronyssinus. B cells were depleted in HDM-sensitized animals to investigate the importance of B cells in maintenance of the allergic response. B cells were depleted before HDM sensitization to investigate the role of B cells in T-cell priming; furthermore, HDM sensitization was performed in mice with MHC class II expression restricted to the B-cell lineage. RESULTS: We found that B cells serve as potent antigen-presenting cells ex vivo and restimulate in vivo-primed HDM-specific TH cells. HDM antigens were taken up by B cells independently of B-cell receptor specificity, indicating that HDM uptake and antigen presentation to CD4+ T cells is not restricted to rare B cells carrying HDM-specific B cell receptors. B-cell depletion before HDM challenge in HDM-sensitized mice resulted in a dramatic reduction of allergic response, indicating the role of B cells in amplification of TH2 responses. In contrast, HDM sensitization of mice in which MHC class II expression was restricted to B cells revealed the inability of these cells to prime TH2 responses but highlighted their unexpected role in priming TH1 and TH17 responses. CONCLUSION: Collectively, these data reveal new mechanisms leading to initiation and exacerbation of the allergic response that might have implications for designing new therapeutic strategies to combat HDM allergy.
BACKGROUND: The importance of B lymphocytes to present antigens for antibody production is well documented. In contrast, very little is known about their capacity to influence CD4+ T-cell activation during a primary or secondary response to allergens. OBJECTIVE: Using mouse models of asthma, we investigated the role of B cells as antigen-presenting cells in priming and maintenance of TH cell responses. METHODS:Mice were immunized through the intranasal route with house dust mite (HDM) extract derived from Dermatophagoides pteronyssinus. B cells were depleted in HDM-sensitized animals to investigate the importance of B cells in maintenance of the allergic response. B cells were depleted before HDM sensitization to investigate the role of B cells in T-cell priming; furthermore, HDM sensitization was performed in mice with MHC class II expression restricted to the B-cell lineage. RESULTS: We found that B cells serve as potent antigen-presenting cells ex vivo and restimulate in vivo-primed HDM-specific TH cells. HDM antigens were taken up by B cells independently of B-cell receptor specificity, indicating that HDM uptake and antigen presentation to CD4+ T cells is not restricted to rare B cells carrying HDM-specific B cell receptors. B-cell depletion before HDM challenge in HDM-sensitized mice resulted in a dramatic reduction of allergic response, indicating the role of B cells in amplification of TH2 responses. In contrast, HDM sensitization of mice in which MHC class II expression was restricted to B cells revealed the inability of these cells to prime TH2 responses but highlighted their unexpected role in priming TH1 and TH17 responses. CONCLUSION: Collectively, these data reveal new mechanisms leading to initiation and exacerbation of the allergic response that might have implications for designing new therapeutic strategies to combat HDM allergy.
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