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2015 ; 192
(6
): 695-705
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B Cell-Activating Factor An Orchestrator of Lymphoid Follicles in Severe Chronic
Obstructive Pulmonary Disease
#MMPMID26073875
Polverino F
; Cosio BG
; Pons J
; Laucho-Contreras M
; Tejera P
; Iglesias A
; Rios A
; Jahn A
; Sauleda J
; Divo M
; Pinto-Plata V
; Sholl L
; Rosas IO
; Agustí A
; Celli BR
; Owen CA
Am J Respir Crit Care Med
2015[Sep]; 192
(6
): 695-705
PMID26073875
show ga
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-?B (NF-?B).
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-?B 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.
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