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Researchers reveal selection process for development of immune system
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Researchers from the National Jewish health research team recently reported that the immune system uses a selection process that has both positive and negative signals to create an effective population of B cells, and a flaw in the selection process can contribute to autoimmunity or immune deficiency.
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.
Using a mouse model and an in vitro system designed specifically for B cells, the researchers concluded 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.
The research team activated the protein Erk by turning on the Ras gene, and saw that more B cells escaped the bone marrow to mature. However, 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, the researchers concluded.
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