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Researchers discover fundamental step in immune-system development
Date:3/24/2010

Researchers at National Jewish Health have discovered a fundamental step in the development of the immune system, one that allows B cells to mature and fight disease by producing effective antibodies. Immunologist Roberta Pelanda, PhD, and her colleagues have demonstrated that immature B cells in the bone marrow must receive a positive signal before they can migrate to the spleen where they mature and are activated. In the March 15, 2010 issue of The Journal of Experimental Medicine, the researchers also reported that a protein known as Erk helps deliver that positive signal.

"Our work demonstrates that the immune system uses both positive and negative selection processes to create an effective population of B cells," said Dr. Pelanda, Associate Professor in the Integrated Department of Immunology at National Jewish Health and the University of Colorado Denver. "A defect in either selection process could lead to autoimmunity or immune deficiency."

Humans make millions of B cells every day, each one equipped with its own unique B-cell receptor. Each receptor recognizes a specific protein fragment. Once the receptor recognizes that fragment, the B cell becomes activated and releases antibodies that attack the protein or the cell it is on.

B-cell receptors first appear on developing B cells in the bone marrow. Some of those receptors bind to proteins that are a normal part of the body, and could trigger an autoimmune attack. Other receptors can be non-functional. The selection process weeds out these dangerous and non-functional B cells to produce a population that can recognize a wide variety of foreign, potentially harmful invaders, but tolerate proteins that are a normal part of the organism.

Negative selection occurs in the bone marrow when potentially autoimmune B cells are detected, rejected and instructed to produce a different receptor.

The next step has been unclear. Do B cells that survive negative selection leave
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Contact: William Allstetter
allstetterw@njhealth.org
303-398-1002
National Jewish Medical and Research Center
Source:Eurekalert

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