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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Available from: Ingo Hilgendorf
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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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    ABSTRACT: Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.
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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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