title: 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 (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). 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 analysed B cells from NP or tonsil, or after ILC2 coculture, 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 extrafollicular marker Epstein-Barr virus-induced protein 2 (EBI2), but significantly fewer germinal centre (GC) B cells compared with 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
  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.
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Feldman
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kasjanski
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Poposki
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hernandez
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Chen
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Norton
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Suh
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Carter
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Stevens
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Peters
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Kern
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Conley
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shintani-Smith
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Welch
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Grammer
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Harris
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: A
authors.identifier: http://orcid.org/0000-0001-9144-3138
authors.initials: A
authors.lastname: Kato
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Schleimer
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Hulse
mesh_terms: D000917:Antibody Formation / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C080105:GPR183 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: 
  ENT
  ; B cells; IgE; lymphocytes