A Role for B Cells in Organic Dust Induced Lung Injury

RATIONALE: 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 injury is unknown, yet might be relevant given the emerging role of B cells in obstructive airways disease and associated autoimmunity.

METHODS: Using an established intranasal inhalation exposure model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were treated daily with saline or swine confinement organic dust extract (ODE) for 3 weeks. Bronchoalveolar lavage fluids, lung tissues, and serum were collected. Cytokines analyzed by ELISA; cellular influx by flow cytometry. Serum collected to measure immunoglobulins and autoantibody responses. Lung tissues stained for modified self-proteins.

RESULTS: ODE-induced neutrophil influx 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. 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. Serum IgG responses, anti-citrullinated protein antibody (ACPA), and anti-malondialdehyde-acetaldehyde (MAA) autoantibody responses were increased in ODE treated WT mice vs. 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.

CONCLUSIONS: Agriculture organic dust induced lung injury is dependent upon B cells, and this exposure induces autoreactive immune responses to citrullinated and MAA-modified proteins implicated in the systemic autoimmune pathogenesis.