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However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content> patients develop nasal polyps (<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>s), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (<jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2s). We have reported that <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> contain elevated levels of B cells and antibodies, making <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> an ideal system for studying B cells in the airways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed B cells from <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> or tonsil, or after <jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2 coculture, by flow cytometry. Antibody production from tissue was measured using Luminex assays and the frequency of antibody\u2010secreting cells by <jats:styled-content style=\"fixed-case\">ELIS<\/jats:styled-content>pot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> contained significantly elevated frequencies of plasmablasts, especially those that expressed the extrafollicular marker Epstein\u2013Barr virus\u2010induced protein 2 (<jats:styled-content style=\"fixed-case\">EBI<\/jats:styled-content>2), but significantly fewer germinal centre (<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>) B cells compared with tonsil. Antibody production and the frequency of antibody\u2010secreting cells were significantly elevated in <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>, and there was evidence for local class switch recombination in <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>. Finally, <jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2s directly induced <jats:styled-content style=\"fixed-case\">EBI<\/jats:styled-content>2 expression on B cells <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>Our data suggest there is a unique B cell activation environment within <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> that is distinct from classic <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010mediated mechanisms. We show for the first time that <jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2s directly induce <jats:styled-content style=\"fixed-case\">EBI<\/jats:styled-content>2 expression on B cells, indicating that <jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2s may play an important role in B cell responses. B cell\u2010targeted therapies may provide new treatment options for <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12878","type":"journal-article","created":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T13:56:48Z","timestamp":1482328608000},"page":"457-466","source":"Crossref","is-referenced-by-count":64,"title":["Chronic airway inflammation provides a unique environment for B cell activation and antibody production"],"prefix":"10.1111","volume":"47","author":[{"given":"S.","family":"Feldman","sequence":"first","affiliation":[{"name":"Division of Allergy\u2010Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Kasjanski","sequence":"additional","affiliation":[{"name":"Division of Allergy\u2010Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Poposki","sequence":"additional","affiliation":[{"name":"Division of Allergy\u2010Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. N.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Allergy\u2010Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. E.","family":"Norton","sequence":"additional","affiliation":[{"name":"Division of Allergy\u2010Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Suh","sequence":"additional","affiliation":[{"name":"Division of Allergy\u2010Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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