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Protective role of B cells in sterile particulate-induced lung injury.

ABSTRACT: Susceptibility to chronic beryllium (Be) disease is linked to HLA-DP molecules possessing a glutamic acid at the 69th position of the ?-chain (?Glu69), with the most prevalent ?Glu69-containing molecule being HLA-DP2. We have previously shown that HLA-DP2 transgenic (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 mice, B cells also accumulate in the lungs of CBD subjects, located at the periphery and surrounding the granuloma. Overall, our data suggest 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.

SUBMITTER: Atif SM

PROVIDER: S-EPMC6629102 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Protective role of B cells in sterile particulate-induced lung injury.

Atif Shaikh M SM Mack Douglas G DG McKee Amy S AS Rangel-Moreno Javier J Martin Allison K AK Getahun Andrew A Maier Lisa A LA Cambier John C JC Tuder Rubin R Fontenot Andrew P AP

JCI insight 20190516

Susceptibility to chronic beryllium (Be) disease 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 (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 ...[more]

PMID: 31094704

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Protective role of B cells in sterile particulate-induced lung injury.

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Protective role of B cells in sterile particulate-induced lung injury.

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