Role of B cells in T helper cell responses in a mouse model of asthma

Publication date: Available online 7 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Tomasz Piotr Wypych, Roberta Marzi, Gregory F. Wu, Antonio Lanzavecchia, Federica Sallusto
BackgroundThe 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 primary or secondary response to allergens.ObjectiveUsing mouse models of asthma, we investigated the role of B cells as antigen presenting cells in propagation and initiation of T helper cell responses.MethodsMice were immunized via intranasal route with house dust mite extract (HDM) derived from Dermatophagoides pteronyssinus. To investigate the importance of B cells in maintenance of allergic response, B cells were depleted in HDM-sensitized animals. To investigate the role of B cells in T cell priming, B cells were depleted before HDM sensitization; furthermore, HDM sensitization was performed in mice with MHC-II expression restricted to the B cell lineage.ResultsWe found that B cells serve as potent antigen presenting cells ex-vivo and restimulate in vivo-primed HDM-specific T helper cells. HDM antigens were taken up by B cells independently of the 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-II expression was restricted to B cells revealed the inability of these cells to initiate Th2 responses, but highlighted their unexpected role in priming Th1 and Th17 responses.ConclusionCollectively, these data reveal new mechanisms leading to initiation and exacerbation of allergic response that may have implications for designing new therapeutic strategies to combat house dust mite allergy.

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Teaser

B cells efficiently take up HDM antigens independently of their B cell receptor specificity and serve as potent antigen presenting cells, influencing both propagation and initiation of T helper cell response in vivo.


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