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

the bone marrow on their own? Or do they need a signal that tells them to leave the marrow and migrate to the spleen?

Dr. Pelanda and her colleagues knew that B-cell receptors deliver a constant, or 'tonic,' signal, even when they are not activated. They thought that tonic signal might direct appropriate B cells to leave the bone marrow, migrate to the spleen and mature.

Using a unique mouse model and an in vitro system designed specifically for B cells, Dr. Pelanda found that mice who make fewer B-cell receptors have fewer mature B cells in their spleens. The B cells could have left the bone marrow but died because they did not have a B-cell receptor, known to be necessary for survival. If that were the case, then a pro-survival factor, bcl-2, should have rescued mature B cells and increased their population. It did not. Thus, it became clear that immature B cells must receive a signal from the B-cell receptor that allows them to escape the bone marrow, migrate and mature.

"It is a very important checkpoint," said Dr. Pelanda. "Without it, B cells are stuck in the bone marrow, unable to circulate, mature and contribute to immune defense."

Dr. Pelanda and her colleagues then activated the protein Erk by turning on the Ras gene, and saw that more B cells escaped the bone marrow to mature. Conversely, when they blocked activation of Erk in normal B cells, few were able to mature. Thus, Erk helps deliver the positive-selection signal that allows B cells to mature.


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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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