The Important Protector Against Sepsis, scientists have discovered a previously unknown type of immune cell, a B cell that can produce the important growth factor GM-CSF, which stimulates many other immune cells. They also found that these novel cells may help protect against the overwhelming, life-threatening immune reaction known as sepsis.
"B cells are a relatives of white blood cells that secrete antibodies, & GM-CSF induces the production or activation of granulocytes & macrophages, other white blood cells that have specific roles in the immune technique," says Filip Swirski, PhD, of the MGH Middle for Systems Biology, senior author of the document that is to be published in the journal Science & is receiving advance release on the Science Express web-site. "Our findings are surprising not only because B cells were not historicallyin the past known to produce GM-CSF in vivo but also because they indicate these novel cells initiate an important immune response."
As part of a separate inquiry, Swirski & his team analyzed production of GM-CSF (granulocyte macrophage colony-stimulating factor) in tissue from several important organs. They were surprised to find that application of a bacterial molecule known to produce a powerful immune response induced GM-CSF production by what turned out to be a historicallyin the past unknown relatives of B cells in the spleen. Because GM-CSF is known to activate white blood cells as part of the innate immune response - the body's first line defence against pathogens - the novel cells were named innate response activator (IRA) B cells.
The researchers went on to identify distinguishing characteristics of IRA-B cells, including gene expression patterns not seen in other B cells. They also determined that IRA-B cells derive from B cells known as B1a B cells. These IRA-B cell precursors originally reside in the peritoneal cavity but, after detecting the presence of invading bacteria, travel to the spleen or bone marrow where they differentiate in to IRA-B cells that can either produce antibodies or release GM-CSF.
"While the IRA-B cell shares plenty of attributes with other B cells, it is distinctive in its involvement with GM-CSF production," explains Clinton Robbins, PhD, co-lead author of the Science news story. "Instead of the classic way that B cells recognize antigens, B1a B cells produce IRA-B cells after recognizing bacteria by a kind of receptor known to be involved in the first steps of inflammation. The IRA-B cell, therefore, appears to be an early orchestrator of the immune technique."
"We think that IRA-B cells sound a distress call when they deliver GM-CSF to the spleen, an organ where cells known to be important to the recognition & clearance of bacteria reside," explains Swirski, an immunologist who is an assistant professor of Radiology at Harvard Medical School. "Sepsis is an immunological conundrum. On the hand it results from failure of the immune technique to control infection. On the other hand, immune cells that do reply inflict destroy & contribute to complications such as leakage of blood vessel walls & septic shock.
To check the potential role of IRA-B cells in sepsis, the researchers developed a mouse model in which B cells were unable to produce GM-CSF, stopping the generation of IRA-B cells. Those mice were unable to mount a defense against induced sepsis & died much earlier & in greater numbers than did control animals. Inflammatory markers in the infected mice lacking IRA-B cells suggested a defect in the ability to clear bacteria.
Sepsis - is a potentially deadly medical condition that is characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) and the presence of a known or suspected infection.[1][2] The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues. A lay term for sepsis is blood poisoning, also used to describe septicaemia. Severe sepsis is the systemic inflammatory response, plus infection, plus the presence of organ dysfunction.
