Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis.
Bottom Line: We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M (IgM).The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early frontline defense against bacteria invading the lungs.The study describes a previously unrecognized GM-CSF-IgM axis and positions IRA B cells as orchestrators of protective IgM immunity.
Affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Visceral, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany email@example.com firstname.lastname@example.org.Show MeSH
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Mentions: Previously, we demonstrated that the human spleen contains a population of GM-CSF–producing IRA B-like cells (Rauch et al., 2012). To determine whether humans also contain, or can develop, IRA B-like cells in the pleural space, we obtained human pleural fluid by thoracentesis, and cultured B cells in either medium or a classical human B cell stimulation cocktail containing anti-Ig and IL-2. After 2 d of culture, human pleural CD19+ CD20+ IgM+ B cells produced GM-CSF (Fig. 10, A–C). The GM-CSF producers clustered in a single rather than bimodal distribution, suggesting indiscriminate activation in this in vitro setting. To reveal whether the appearance of IRA B-like cells was unique to the pleural space, we also cultured B cells from cord and peripheral blood. In the cord blood, which contains predominantly naive and transitional cells, a large GM-CSF–producing population likewise arose (Fig. 10 C). In contrast, culturing peripheral blood B cell did not stimulate GM-CSF production (Fig. 10 C), a result which supports the concept that IRA B cells arise in specific locations. Adding nontoxic doses of anti–GM-CSF, anti-CD116, or a STAT5 inhibitor to the culture containing pleural cells prevented the appearance of IRA B-like cells, further indicating an important role of the GM-CSF pathway (Fig. 10 D). Although further work is required to elucidate the similarities and differences between murine and human IRA B cells, these data nevertheless illustrate our current findings’ potential translatability. In sum, the production of GM-CSF by IRA B cells orchestrates the generation of protective IgM, which is critical in the early defense to infection (Fig. 10 E).
Affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Visceral, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany email@example.com firstname.lastname@example.org.