A role for B cells in organic dust induced lung inflammation

Abstract

BackgroundAgriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity.MethodsUsing an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected.ResultsODE-induced neutrophil influx in lavage fluid was not reduced in BCR KO animals, but there was reduction in TNF-α, IL-6, CXCL1, and CXCL2 release. ODE-induced lymphoid aggregates failed to develop in BCR KO mice. There was a decrease in ODE-induced lung tissue CD11c+CD11b+ exudative macrophages and compensatory increase in CD8+ T cells in lavage fluid of BCR KO animals. Compared to saline, there was an expansion of conventional B2-, innate B1 (CD19+CD11b+CD5+/−)-, and memory (CD19+CD273+/-CD73+/−) B cells following ODE exposure in WT mice. Autoreactive responses including serum IgG anti-citrullinated protein antibody (ACPA) and anti-malondialdehyde-acetaldehyde (MAA) autoantibodies were increased in ODE treated WT mice as compared to saline control. B cells and serum immunoglobulins were not detected in BCR KO animals.ConclusionsLung tissue staining for citrullinated and MAA modified proteins were increased in ODE-treated WT animals, but not BCR KO mice. These studies show that agriculture organic dust induced lung inflammation is dependent upon B cells, and dust exposure induces an autoreactive response.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0703-x) contains supplementary material, which is available to authorized users.

Combined Collagen-Induced Arthritis and Organic Dust-Induced Airway Inflammation to Model Inflammatory Lung Disease in Rheumatoid Arthritis

“…Consistent with articular/bone findings, serum studies demonstrated that coexposure (CIA + ODE) was associated with the greatest levels of pentraxin‐2, a murine acute‐phase reactant protein, and strikingly, high levels of anti‐CCP antibody. In previous work, we found that inhalant ODE treatment increased the airway expression of citrullinated and MAA‐modified proteins; in addition, we observed low‐grade anti‐CCP and anti‐MAA antibody responses in C57BL/6 mice . In these studies with the arthritis‐susceptible DBA/1J mice, anti‐CCP antibody responses were strikingly augmented in CIA + ODE treated mice.…”

“…Serum from whole blood was collected and pentraxin‐2 (murine acute phase reactant protein) levels were quantified by quantikine ELISA according to manufacturer's instructions (R&D Systems). Anti‐MAA antibodies (IgG) were quantified as previously described . Anticitrullinated peptide antigen (ACPA) was determined using a modification of the second‐generation anti‐CCP antibody ELISA (Diastat; Axis‐Shield Diagnostics, Dundee, UK) as previously described .…”

“…Anti-MAA antibodies (IgG) were quantified as previously described. (22) Anticitrullinated peptide antigen (ACPA) was determined using a modification of the secondgeneration anti-CCP antibody ELISA (Diastat; Axis-Shield Diagnostics, Dundee, UK) as previously described. (30) Concentrations of antibody to mouse type II collagen was determined using ELISA-grade mouse type II collagen as the coating antigen (Chondrex) and detected using an HRP-conjugated goat antimouse antibody specific for IgG (Fcγ-specific; Jackson ImmunoResearch, West Grove, PA, USA).…”

“…The limitation of this model is that the SKG mice do not develop autoimmunity or arthritis following inhalation injury (ie, tobacco smoke or bleomycin), which had been interpreted to suggest that lung injury/inflammation alone is not sufficient to induce arthritis . In our established animal model (C57BL/6 strain) of agriculture‐related organic dust extract (ODE) exposure‐induced airway inflammatory disease, we recently discovered evidence that ODE induced citrullinated and malondialdehyde‐acetaldehyde‐ (MAA‐) modified lung proteins with associated systemic autoantibody responses . This is relevant because anticitrullinated protein antibody (ACPA) and anti‐MAA antibody responses have been shown to characterize RA .…”

The Effect of Inhalant Organic Dust on Bone Health

“…TNF-α, IL-6, neutrophil chemoattractants), Th1/Th17 microenvironment, activation of macrophages, and lung pathology marked by lymphoid aggregates and peribronchial and perivascular inflammation (21,22,23,31,32,). It was recently reported that there is also a role for B cells in ODE-induced airway inflammation with further evidence for an autoreactive response marked by increased levels of IgG anti-citrullinated protein antibody and anti-malondialdehyde-acetaldehyde autoantibodies (24). Homeostatic regulators of the ODE-induced airway inflammatory process include protein kinase C epsilon (PKCε) (33), nucleotide-binding oligomerization domain 2 (NOD2) (34,35), and scavenger receptor class A (SRA) (36).…”