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: 31.48). 02/2012; 335(6068):597-601. DOI: 10.1126/science.1215173
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Ingo Hilgendorf, Jul 07, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: B lymphocytes promote the initial innate interferon response to viral pathogens without the need for antigen receptor activation. B cell dependent IFN production requires the cytokine, lymphotoxin-β. The LTβ pathway is well known to regulate lymphoid organogenesis and homeostasis by differentiating stromal cells and macrophages. However, in response to viral pathogens these same B cell-regulated populations rapidly produce type 1 interferons. Thus, B cells act as innate effector cells via LTβ homeostatic pathways, which serve as innate host barriers to viral pathogens.
    08/2012; 1. DOI:10.12688/f1000research.1-8.v1
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The immune system develops in waves during ontogeny; it is initially populated by cells generated from fetal hematopoietic stem cells (HSCs) and later by cells derived from adult HSCs. Remarkably, the genetic programs that control these two distinct stem cell fates remain poorly understood. We report that Lin28b is specifically expressed in mouse and human fetal liver and thymus, but not in adult bone marrow or thymus. We demonstrate that ectopic expression of Lin28 reprograms hematopoietic stem/progenitor cells (HSPCs) from adult bone marrow, which endows them with the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta (γδ) T cells, and natural killer T (NKT) cells.
    Science 03/2012; 335(6073):1195-200. DOI:10.1126/science.1216557 · 31.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In North America, approximately 700,000 cases of sepsis occur each year, with mortality ranging between 30% and 50%. The American Journal of Pathology has featured numerous articles on the topic, revealing mechanistic insights gleaned from both experimental rodent models and human sepsis. Nonetheless, there remains urgent need to determine the basis for sepsis-related complications and how they can be avoided, as well as how they can be most effectively treated once recognized. This historical perspective reviews what we currently understand about the mechanisms of sepsis, as well as the barriers that remain in our treatment strategies.
    American Journal Of Pathology 05/2012; 181(1):2-7. DOI:10.1016/j.ajpath.2012.05.003 · 4.60 Impact Factor