Chronic airway inflammation provides a unique environment for B cell activation and antibody production

Abstract

Background B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NP), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways. Objective We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation. Methods We analyzed B cells from NP or tonsil, or after ILC2 co-culture, by flow cytometry. Antibody production from tissue was measured using Luminex assays, and the frequency of antibody-secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT-PCR. Results NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extra follicular marker Epstein-Barr virus-induced protein 2 (EBI2), but significantly fewer germinal center (GC) B cells compared to tonsil. Antibody production and the frequency of antibody-secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro. Conclusions and Clinical Relevance Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC-mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell-targeted therapies may provide new treatment options for CRSwNP.

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

“…40,42 However, Feldman and collaborators did not detect an elevation of follicles or large clusters of lymphoid cells in their studies in Chicago. 43 In addition, large increases in extrafollicular plasmablasts expressing the marker Epstein-Barr virus-induced protein 2 have been reported by Hulse and her colleagues, suggesting that some B cells are activated outside of germinal centers in CRS tissues. 43 This could result in the emergence of autoreactive antibody producing cells, as reported by Tan et al 44 Whether the causative antigens driving local immunoglobulin production in nasal polyps are exogenous or self antigens or both has not been completely clarified.…”

“…43 In addition, large increases in extrafollicular plasmablasts expressing the marker Epstein-Barr virus-induced protein 2 have been reported by Hulse and her colleagues, suggesting that some B cells are activated outside of germinal centers in CRS tissues. 43 This could result in the emergence of autoreactive antibody producing cells, as reported by Tan et al 44 Whether the causative antigens driving local immunoglobulin production in nasal polyps are exogenous or self antigens or both has not been completely clarified. In Caucasian patients with CRSwNP, it has been reported that Staphylococcus aureus enterotoxins, acting as both antigens and superantigens, may drive local IgE production.…”

Innate lymphoid cells and allergic disease

“…96 In humans, ILC2 promote B cell extrafollicular responses as evidenced by increased B cell expression of EBI2 in human ILC2:B cell co-culture. 97 These data suggest ILC2 may influence the B cell and/or IgE compartments in allergic disease. 98 ILC2 also coordinate with cells of the innate immune system.…”

Розвиток Імунної Відповіді При Стафілококовій Пневмонії (Частина 8)

“…Экстрафолли-кулярный антительный ответ характерен для ран-ней стадии инфекционного процесса и может осу-ществляться с помощью или без помощи Т-клеток [19]. Экстрафолликулярные плазматические клетки являются короткоживущими клетками и не обес-печивают долгосрочной продукции антибактери-альных антител.…”