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

S. Feldman, R. Kasjanski, J. Poposki, D. Hernandez, J. N. Chen, J. E. Norton, L. Suh, R. G. Carter, Whitney Stevens, Anju Tripathi Peters, Robert C Kern, David B Conley Jr, Bruce Kuang-Huay Tan, Stephanie Shintani Smith, Kevin Christian Welch, Leslie C Grammer III, K. E. Harris, Atsushi Kato, Robert P Schleimer, Kathryn E Hulse*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)457-466
Number of pages10
JournalClinical and Experimental Allergy
Volume47
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Antibody Formation
B-Lymphocytes
Nasal Polyps
Inflammation
Antibody-Producing Cells
Germinal Center
Palatine Tonsil
Viruses
Genetic Recombination
Proteins
Cell- and Tissue-Based Therapy
Coculture Techniques
Eosinophils
Flow Cytometry
Immunohistochemistry
Lymphocytes
Gene Expression
Polymerase Chain Reaction

Keywords

  • B cells
  • ENT
  • IgE
  • lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{bd160df1884a45d4ad1164f1faad3c17,
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 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.",
keywords = "B cells, ENT, IgE, lymphocytes",
author = "S. Feldman and R. Kasjanski and J. Poposki and D. Hernandez and Chen, {J. N.} and Norton, {J. E.} and L. Suh and Carter, {R. G.} and Whitney Stevens and Peters, {Anju Tripathi} and Kern, {Robert C} and {Conley Jr}, {David B} and Tan, {Bruce Kuang-Huay} and Smith, {Stephanie Shintani} and Welch, {Kevin Christian} and {Grammer III}, {Leslie C} and Harris, {K. E.} and Atsushi Kato and Schleimer, {Robert P} and Hulse, {Kathryn E}",
year = "2017",
month = "4",
day = "1",
doi = "10.1111/cea.12878",
language = "English (US)",
volume = "47",
pages = "457--466",
journal = "Clinical and Experimental Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Chronic airway inflammation provides a unique environment for B cell activation and antibody production

AU - Feldman, S.

AU - Kasjanski, R.

AU - Poposki, J.

AU - Hernandez, D.

AU - Chen, J. N.

AU - Norton, J. E.

AU - Suh, L.

AU - Carter, R. G.

AU - Stevens, Whitney

AU - Peters, Anju Tripathi

AU - Kern, Robert C

AU - Conley Jr, David B

AU - Tan, Bruce Kuang-Huay

AU - Smith, Stephanie Shintani

AU - Welch, Kevin Christian

AU - Grammer III, Leslie C

AU - Harris, K. E.

AU - Kato, Atsushi

AU - Schleimer, Robert P

AU - Hulse, Kathryn E

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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 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.

AB - 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 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.

KW - B cells

KW - ENT

KW - IgE

KW - lymphocytes

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U2 - 10.1111/cea.12878

DO - 10.1111/cea.12878

M3 - Article

VL - 47

SP - 457

EP - 466

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

IS - 4

ER -