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Role of B cells in TH cell responses in a mouse model of asthma - 05/04/18

Doi : 10.1016/j.jaci.2017.09.001 
Tomasz Piotr Wypych, PhD a, b, , Roberta Marzi, PhD a, Gregory F. Wu, MD, PhD c, Antonio Lanzavecchia, MD a, d, Federica Sallusto, DSc a,
a Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland 
b Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland 
c Department of Neurology, Washington University, St Louis, Mo 
d Institute of Microbiology, ETH Zürich, Zurich, Switzerland 

Corresponding author: Federica Sallusto, DSc, and Tomasz Piotr Wypych, PhD, Institute for Research in Biomedicine, Università della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.Institute for Research in BiomedicineUniversità della Svizzera ItalianaVia Vincenzo Vela 6Bellinzona6500Switzerland

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.

El texto completo de este artículo está disponible en PDF.

Graphical abstract




El texto completo de este artículo está disponible en PDF.

Key words : Mouse model of asthma, house dust mite, B cells, antigen presentation, initiation of allergic response, maintenance of allergic response

Abbreviations used : AF, APC, BAL, BCR, CFSE, DC, HDM, LT, MLN, OVA, TCR


Esquema


 This work was in part funded by the Swiss National Science Foundation (grant n. PDAMP3_137087 and grant n. PDFMP3_137127).
 Disclosure of potential conflict of interest: F. Sallusto's institution received grant PDAMP3_137087 and grant PDFMP3_137127 from the Swiss National Science Foundation, and T. Wypych personally received a travel grant from the European Federation of Immunological Societies (EFIS) for this work. G. F. Wu's institution received grant R01NS083678 from the National Institutes of Health for this work. Dr Sallusto personally received consultancy fees from HUMABS BioMed SA for other works. A. Lanzavecchia declares that he has no relevant conflicts of interest.


© 2017  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 141 - N° 4

P. 1395-1410 - avril 2018 Regresar al número
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