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.

Since their discovery nearly 40 years ago, B-1 cells have continued to challenge the boundaries between innate and adaptive immunity, as well as myeloid and lymphoid functions. This B-cell subset ensures early immunity in neonates before the development of conventional B (B-2) cells and respond to immune injuries throughout life. B-1 cells are multifaceted and serve as natural- and induced-antibody-producing cells, phagocytic cells, antigen-presenting cells, and anti-/pro-inflammatory cytokine-releasing cells. This review retraces the origin of B-1 cells and their different roles in homeostatic and infectious conditions before focusing on pollutants comprising contact-sensitivity-inducing chemicals, endocrine disruptors, aryl hydrocarbon receptor (AHR) ligands, and reactive particles.