Abstract

Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH−/− mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH−/− mice. The allergen-induced expansion of CD4+ T cells was impaired in the lungs and draining lymph nodes of JH−/− mice. Furthermore, lymphocytes from JH−/− mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation in vitro. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.

Highlights

  • Asthma is a complex and heterogeneous disease of the airways that affects millions of people worldwide

  • We used house dust mite (HDM), Alternaria, and Aspergillus, which are associated with treatment-resistant asthma and are commonly found in homes [2,13,14,15]

  • Multiple exposures to OAAH induced a robust increase in bronchoalveolar lavage (BAL) eosinophils at 2 weeks, and eosinophils made up approximately 80% of total BAL cells (Fig. 1B)

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Summary

Introduction

Asthma is a complex and heterogeneous disease of the airways that affects millions of people worldwide. Airway inflammation in asthma is often triggered by the exposure to environmental allergens, such as molds and arthropods. Concurrent exposure to several airborne allergens is common [1], and exposures to multiple allergens are significantly associated with asthma development [2]. Certain allergens, such as Alternaria and the house dust mite (HDM), are PLOS ONE | DOI:10.1371/journal.pone.0121660. Animal models of asthma that reflect the natural environmental exposure in humans may provide valuable information to understand the pathophysiological mechanisms of the disease

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