Innate Response Activator B Cells Protect Against Microbial Sepsis

Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Science (Impact Factor: 33.61). 02/2012; 335(6068):597-601. DOI: 10.1126/science.1215173
Source: PubMed


Recognition and clearance of a bacterial infection are a fundamental properties of innate immunity. Here, we describe an effector
B cell population that protects against microbial sepsis. Innate response activator (IRA) B cells are phenotypically and functionally
distinct, develop and diverge from B1a B cells, depend on pattern-recognition receptors, and produce granulocyte-macrophage
colony-stimulating factor. Specific deletion of IRA B cell activity impairs bacterial clearance, elicits a cytokine storm,
and precipitates septic shock. These observations enrich our understanding of innate immunity, position IRA B cells as gatekeepers
of bacterial infection, and identify new treatment avenues for infectious diseases.

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    • "It has also been suggested that the precursor of the earliest B1a progenitors is yet to be described, and it remains possible that these cells represent a vestigial wave of B cell development similar to one seen during foetal erythropoiesis [34]. Adult B1a cells were recently shown to give rise to a further lineage, ‘immune response activator’ (IRA) cells, that is the source of granulocyte-colony stimulating factor (GM-CSF) and important in protecting against sepsis [16]. "
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    • "Recently, it has been proposed that B cells are involved in the early innate immune response during experimental bacterial sepsis [101] and Darton et al. reported that adults who have recovered from an episode of invasive pneumococcal disease demonstrate defective B-cell activation [106]. More recently, Rauch et al. have demonstrated that innate response activator B cells (IRA-B cells) play a critical role in the response to sepsis, as mice lacking B-cell-derived GM-CSF are unable to clear bacteria, elicit exaggerated inflammatory responses, and, more likely, succumb to infection [107]. Moreover, they have already developed an in vitro system to expand IRA-B cells from their precursors and then inject them into the patient to boost their immune response [108]. "
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    • "These cells belong to the innate defense system, they contain large cytoplasmic stores of IgM antibodies and they are the main effectors of the rapid release of IgM. IRA B cells are depleted in experimental sepsis and this leads to early death [17]. The evidence coming from experimental animal data may help explain the importance of the ex vivo production of IgM from our patient population. "
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