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: At this point, the data can be summarized as follows: in response to pulmonary infection, IRA B cells arise in the pleural space and lung; in the absence of IRA B cells (absence of B cell–derived GM-CSF), mice fail to produce IgM and succumb to pneumonia; and pulmonary infection mobilizes pleural B1a B cells, which relocate to the lung and produce IgM. To further validate these findings, we wished to test the importance of pleural B cell–derived GM-CSF and secreted IgM in our model. We pursued a rescue strategy involving the adoptive transfer of different cell populations to the pleural spaces of GM/µMT mice. We transferred Csf2−/− pleural B cells, WT pleural non–B cells, pleural B cells from secretory IgM-deficient (sIgM−/−) mice, and WT pleural B cells (Fig. 9 A). Comparing the adoptive transfer of WT pleural B cells with Csf2−/− pleural B cells and WT pleural non–B cells allowed us to determine the importance of B cell–derived GM-CSF, whereas sIgM−/− mice demonstrated the importance of secreted IgM. Mice that received WT pleural B cells into the pleural space were healthier, as judged by their clinical scores, body temperatures, and bacterial titers (Fig. 9 B). Moreover, mice that received WT pleural B cells had increased titers of IgM (Fig. 9 B). That none of the other three strategies protected the animals indicated that B cell–derived GM-CSF is essential. To determine whether polyclonal IgM could indeed rescue IRA B cell–deficient, GM/µMT chimeras, we injected polyclonal IgM i.t. into GM/µMT mice infected with a high dose of E. coli. Compared with controls receiving PBS, poly-IgM recipients were protected (Fig. 9 C).
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.