The online version of this article (https://doi.org/10.1186/s12931-017-0703-x) contains supplementary material, which is available to authorized users.
Agriculture 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.
Using 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.
ODE-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.
Lung 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.
Additional file 1: Figure S1. Merged confocal images of isotype control antibodies with all 3 channels on each lung tissue section from WT and BCR KO mice treated repetitively with saline or ODE. Zenon 405 labeled rabbit IgG (401 nm to 421 nm) as control for MAA staining, mouse IgM+ anti-mouse IgM Cy3 (550 nm to 570 nm) as control for CIT staining, and ALEXA FLUOR® 594 Conjugated Rabbit IgG as control for CD68 macrophage staining. (PPTX 350 kb)
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- A role for B cells in organic dust induced lung inflammation
Jill A. Poole
Ted R. Mikuls
Michael J. Duryee
Kristi J. Warren
Todd A. Wyatt
Amy J. Nelson
Debra J. Romberger
William W. West
Geoffrey M. Thiele
- BioMed Central
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