Mouse innate-like B-1 lymphocytes promote inhaled particle-induced in vitro granuloma formation and inflammation in conjunction with macrophages

Abstract

The current paradigm for explaining lung granulomatous diseases induced by inhaled particles is mainly based on macrophages. This mechanism is now challenging because B lymphocytes also infiltrate injured tissue, and the deficiency in B lymphocytes is associated with limited lung granulomas in silica-treated mice. Here, we investigated how B lymphocytes respond to micro- and nanoparticles by combining in vivo and in vitro mouse models. We first demonstrated that innate-like B-1 lymphocytes (not conventional B-2 lymphocytes or plasma cells) specifically accumulated during granuloma formation in mice instilled with crystalline silica (DQ12, 2.5 mg/mouse) and carbon nanotubes (CNT Mitsui, 0.2 mg/mouse). In comparison to macrophages, peritoneal B-1 lymphocytes purified from naïve mice were resistant to the pyroptotic activity of reactive particles (up to 1 mg/mL) but clustered to establish in vitro cell/particle aggregates. Mouse B-1 lymphocytes (not B-2 lymphocytes) in coculture with macrophages and CNT (0.1 µg/mL) organized three-dimensional spheroid structures in Matrigel and stimulated the release of TIMP-1. Furthermore, purified B-1 lymphocytes are sensitive to nanosilica toxicity through radical generation in culture. Nanosilica-exposed B-1 lymphocytes released proinflammatory cytokines and alarmins. In conclusion, our data indicate that in addition to macrophages, B-1 lymphocytes participate in micrometric particle-induced granuloma formation and display inflammatory functions in response to nanoparticles.

Differential immunological effects of silica nanoparticles on peripheral blood mononuclear cells of silicosis patients and controls

“…On this basis, we speculate that B cells may play a prominent role in the pathogenesis of silicosis. Similar to our observations, animal experimental studies have identified that B cells, specifically B-1 lymphocytes, respond to inorganic particles like silica by migrating towards the inflammatory site, engaging in phagocytosis alongside macrophages to engulf particles and partake in granuloma formation by organizing inorganic particle-induced cellular aggregation into three-dimensional granulomatous structures ( 25 ).…”

B-1 cells in immunotoxicology: Mechanisms underlying their response to chemicals and particles

“…Unlike macrophages, B-1 cells are resistant to the cytotoxicity of microparticles. This suggests that B-1 cells take advantage of their unique resistance to the toxicity of particles and cluster them, acting as a shield to protect the surrounding cells and avoid particle distribution in the tissue (Hiéronimus et al, 2021) (Figure 3). B-1 cells also interact with their environment, cross-talk, and fuse with macrophages to form compact cellular aggregates in response to pathogens (Vigna et al, 2006;Russo and Mariano, 2010).…”

“…B-1 cells have been implicated in the formation of granulomas triggered by inorganic foreign bodies. Granuloma-inducing particles [silica ( Hiéronimus et al, 2021 ), carbon nanotubes ( Hiéronimus et al, 2021 ) and asbestos ( Pfau et al, 2014a ; Pfau et al, 2014b )] specifically activate and lead to the migration of B-1 cells. They are recruited to and accumulate in the inflammatory site and lymphoid organ when granuloma formation is in progress.…”

“…They are recruited to and accumulate in the inflammatory site and lymphoid organ when granuloma formation is in progress. B-1 cells remain in these organs during particle-induced chronic responses ( Pfau et al, 2014a ; Pfau et al, 2014b ; Hiéronimus et al, 2021 ). Mechanistically, a novel and peculiar property of B-1 cells has been demonstrated as they cluster granuloma-inducing particles.…”

“…MZ B cells are localized in the secondary lymphoid organs and provide antibodies against circulating blood-borne pathogens ( Martin et al, 2001 ). B-1 cells reside primarily in the mesothelial (peritoneal and pleural) cavities, representing the majority (up to 80%) of the B cells ( Marcos et al, 1989 ; Kroese et al, 1992 ; Ghosn et al, 2010 ; Hiéronimus et al, 2021 ). Finally, among innate B cells, regulatory B cells (B reg) are those that reduce the level of inflammation and act as immunosuppressive cells ( Dasgupta et al, 2020 ).…”