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: The leukocyte profile and the differences between the two delivery routes suggested that the pleural space was the preferential source of lung-accumulating serosal B cells. B1a B cells retrieved from the lung contained large reservoirs of IgM (Fig. 8, A and B), which they secreted locally, as measured by ELISPOT assays performed on GFP+ cells that had relocated from the pleural space to lung tissue (Fig. 8 C). To determine the importance of pleural B cells to the host response, we profiled mortality in WT and µMT (i.e., B cell–deficient) mice infected with a high dose of E. coli. After 48 h, ∼40% of WT mice died but ∼60% completely recovered. In contrast, ∼80% of B cell–deficient µMT mice died within 12 h (Fig. 8 D). Additionally, we used ICAPS to transfer pleural B cells from WT mice to the pleural spaces of µMT mice. The µMT pleural B cell recipients, which now contained B cells but only in the pleural space, were then infected with E. coli. Remarkably, this B cell supplementation completely reversed the severe mortality otherwise observed in µMT mice (Fig. 8 D). For controls, we transferred pleural B cells from Csf2−/− mice to the pleural spaces of µMT mice and B cells sorted from the blood of WT mice to the blood (by i.v.) of µMT mice. Neither approach rescued the µMT mice, indicating that GM-CSF produced by pleural B cells was required for protection. The data show that pleural B cells defend against pneumonia.
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.