D2.112 - The Impact of Inflammation on Protective Immune Responses in the Airways

B cells carry out immunosurveillance throughout the body and can reside at barrier sites including the airways where they protect against infectious pathogens by producing antibodies. The airways are frequently exposed to respiratory pathogens and allergens, but in individuals with chronic airway inflammation, dysregulated B cell responses can exacerbate inflammation and result in reduced pathogen clearance and persistent infection. There is a gap in our knowledge of whether chronic airway inflammation is a cause or a consequence of respiratory infection. Effector immune responses against respiratory pathogens can differ according to antibody subclasses; however, the phenotype of respiratory antigen-specific memory B cell subsets have not yet been defined. Furthermore, the consequence of chronic inflammation on the phenotype and function of tissue-resident memory B cells is unknown. 

We have generated a panel of immunodominant antigens from common respiratory pathogens and validated the detection of antigen-specific B cells in tonsil and peripheral blood cells by flow cytometry.

The validation experiments performed with our antigen panel allowed for optimisation of antigen concentrations to detect antigen-specific B cells (Figure 1). We are now extending this approach to characterise respiratory antigen-specific B cells in healthy nasal turbinate and nasal polyp tissue. The properties of tissue-resident memory B cell phenotypes will be compared between health (control turbinates) and chronic inflammation (nasal polyps). We hypothesise that chronic inflammation in the respiratory mucosa alters the phenotype of tissue-resident B cells and impairs local antibody responses to common respiratory pathogens. Therefore, we will compare the frequencies of B cell subsets, transcriptional signatures and their antibody subclass profiles.

This research will aid our understanding of chronic airway inflammation against respiratory pathogens and identify B cells that provide protective responses to guide vaccine design.