TY - JOUR
T1 - B cell-activating factor an orchestrator of lymphoid follicles in severe chronic obstructive pulmonary disease
AU - Polverino, Francesca
AU - Cosio, Borja G.
AU - Pons, Jaime
AU - Laucho-Contreras, Maria
AU - Tejera, Paula
AU - Iglesias, Amanda
AU - Rios, Angel
AU - Jahn, Andreas
AU - Sauleda, Jaume
AU - Divo, Miguel
AU - Pinto-Plata, Victor
AU - Sholl, Lynette
AU - Rosas, Ivan O.
AU - Agustí, Alvar
AU - Celli, Bartolome R.
AU - Owen, Caroline A.
N1 - Publisher Copyright:
Copyright © 2015 by the American Thoracic Society.
PY - 2015/9/15
Y1 - 2015/9/15
N2 - Rationale: Patients with chronic obstructive pulmonary disease (COPD) have increased pulmonary lymphoid follicle (LF) counts. B cell-activating factor of tumor necrosis factor family (BAFF) regulates B cells in health, but its role in COPD pathogenesis is unclear. Objectives: To determine whether BAFF expression in pulmonary LFs correlates with COPD severity, LF size or number, and/or readouts of B-cell function in LFs. Methods: We correlated BAFF immunostaining in LFs in lung explants or biopsies from nonsmoking control subjects (NSC), smokers without COPD (SC), and patients with COPD with the number and size of LFs, and LF B-cell apoptosis, activation, and proliferation. We analyzed serum BAFF levels and BAFF expression in B cells in blood and bronchoalveolar lavage samples from the same subject groups. We assessed whether: (1) cigarette smoke extract (CSE) increases B-cell BAFF expression and (2) recombinant BAFF (rBAFF) rescues B cells from CSE-induced apoptosis by inhibiting activation of nuclear factor-kB (NF-kB). Measurements and Main Results: Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD had increased numbers and larger pulmonary LFs than patients with GOLD stages I-II COPD and SC. We identified two main types of pulmonary LFs: (1) type A, the predominant type in GOLD stages I-II COPD and SC, characterized by abundant apoptotic but few BAFF-positive cells (mostly B cells); and (2) type B, the main type in GOLD stage IV COPD, characterized by abundant BAFF-positive cells but few apoptotic cells (mostly B cells). BAFF levels were also higher in blood and bronchoalveolar lavage B cells in patients with COPD versus NSC and SC. Surprisingly, rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CSE-induced NF-kB activation. Conclusions: Our data support the hypothesis that B-cell BAFF expression creates a self-perpetuating loop contributing to COPD progression by promoting pulmonary B-cell survival and LF expansion.
AB - Rationale: Patients with chronic obstructive pulmonary disease (COPD) have increased pulmonary lymphoid follicle (LF) counts. B cell-activating factor of tumor necrosis factor family (BAFF) regulates B cells in health, but its role in COPD pathogenesis is unclear. Objectives: To determine whether BAFF expression in pulmonary LFs correlates with COPD severity, LF size or number, and/or readouts of B-cell function in LFs. Methods: We correlated BAFF immunostaining in LFs in lung explants or biopsies from nonsmoking control subjects (NSC), smokers without COPD (SC), and patients with COPD with the number and size of LFs, and LF B-cell apoptosis, activation, and proliferation. We analyzed serum BAFF levels and BAFF expression in B cells in blood and bronchoalveolar lavage samples from the same subject groups. We assessed whether: (1) cigarette smoke extract (CSE) increases B-cell BAFF expression and (2) recombinant BAFF (rBAFF) rescues B cells from CSE-induced apoptosis by inhibiting activation of nuclear factor-kB (NF-kB). Measurements and Main Results: Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD had increased numbers and larger pulmonary LFs than patients with GOLD stages I-II COPD and SC. We identified two main types of pulmonary LFs: (1) type A, the predominant type in GOLD stages I-II COPD and SC, characterized by abundant apoptotic but few BAFF-positive cells (mostly B cells); and (2) type B, the main type in GOLD stage IV COPD, characterized by abundant BAFF-positive cells but few apoptotic cells (mostly B cells). BAFF levels were also higher in blood and bronchoalveolar lavage B cells in patients with COPD versus NSC and SC. Surprisingly, rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CSE-induced NF-kB activation. Conclusions: Our data support the hypothesis that B-cell BAFF expression creates a self-perpetuating loop contributing to COPD progression by promoting pulmonary B-cell survival and LF expansion.
KW - Autoimmunity
KW - B cell-activating factor of tumor necrosis factor family
KW - Chronic obstructive pulmonary disease
KW - Cigarette smoke
KW - Lymphoid follicles
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U2 - 10.1164/rccm.201501-0107OC
DO - 10.1164/rccm.201501-0107OC
M3 - Article
C2 - 26073875
AN - SCOPUS:84942242255
SN - 1073-449X
VL - 192
SP - 695
EP - 705
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 6
ER -