Protective role of B cells in sterile particulate–induced lung injury
Shaikh M. Atif, Douglas G. Mack, Amy S. McKee, Javier Rangel-Moreno, Allison K. Martin, Andrew Getahun, Lisa A. Maier, John C. Cambier, Rubin Tuder, Andrew P. Fontenot
Shaikh M. Atif, Douglas G. Mack, Amy S. McKee, Javier Rangel-Moreno, Allison K. Martin, Andrew Getahun, Lisa A. Maier, John C. Cambier, Rubin Tuder, Andrew P. Fontenot
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Research Article Immunology Pulmonology

Protective role of B cells in sterile particulate–induced lung injury

Abstract

Susceptibility to chronic beryllium (Be) disease (CBD) is linked to HLA-DP molecules possessing a glutamic acid at the 69th position of the β-chain (βGlu69), with the most prevalent βGlu69-containing molecule being HLA-DP2. We have previously shown that HLA-DP2–transgenic (HLA-DP2–Tg) mice exposed to Be oxide (BeO) develop mononuclear infiltrates in a peribronchovascular distribution and a beryllium-specific, HLA-DP2–restricted CD4+ T cell response. In addition to T cells, B cells constituted a major portion of infiltrated leukocytes in the lung of BeO-exposed HLA-DP2–Tg mice and sequester BeO particles within ectopic lymphoid aggregates and granulomas. B cell depletion was associated with a loss of lymphoid aggregates and granulomas as well as a significant increase in lung injury in BeO-exposed mice. The protective role of B cells was innate in origin, and BeO-induced B cell recruitment to the lung was dependent on MyD88 signaling. Similar to BeO-exposed HLA-DP2–Tg mice, B cells also accumulate in the lungs of CBD subjects, located at the periphery and surrounding the granuloma. Overall, our data suggest what we believe is a novel modulatory role for B cells in the protection of the lung against sterile particulate exposure, with B cell recruitment to the inflamed lung occurring in an antigen-independent and MyD88-dependent manner.

Authors

Shaikh M. Atif, Douglas G. Mack, Amy S. McKee, Javier Rangel-Moreno, Allison K. Martin, Andrew Getahun, Lisa A. Maier, John C. Cambier, Rubin Tuder, Andrew P. Fontenot

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Figure 7

BeO exposure enhanced acute lung injury in HLA-DP2–Tg mice deficient in B cells.

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BeO exposure enhanced acute lung injury in HLA-DP2–Tg mice deficient in ...
(A and E) Low-magnification view of H&E-stained lung tissue collected from BeO-exposed HLA-DP2–Tg mice treated with isotype control (A) or anti-CD20 (E) mAb is shown. (B and F) Higher-magnification view of A and B is shown. Dark-field microscopic images show BeO particle distribution (white nodules) in the lungs of BeO-exposed mice treated with either isotype control (C) or anti-CD20 (G) mAb. High-magnification view of alveolar tissue in BeO-exposed HLA-DP2–Tg mice treated with isotype control (D) or anti-CD20 (H) mAb is shown. Scale bars: 20 μm. (I) Quantitative analysis of BeO particles within the granuloma and alveolar space. Concentrations of total protein (J), albumin (K), and podoplanin (TIA) (L) measured by ELISA in BALF from isotype control or anti-CD20 mAb–treated BeO-exposed HLA-DP2–Tg mice is shown. Cumulative data from 2 independent experiments having 3 to 5 mice per group are shown, and the mean ± SEM concentration (pg/ml) is shown as a solid line with error bars. Statistical significance was determined using a Student’s t test (2 tailed) (I) or 2-way ANOVA (J–L), and a P value of <0.05 was considered statistically significant.