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Scientists learn the origin of rogue B cells

Doctors have long wondered why, in some people, the immune system turns against parts of the body it is designed to protect, leading to autoimmune disease. Now, researchers at the National Institutes of Health's (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), in collaboration with the Oklahoma Medical Research Foundation, have provided some new clues into one likely factor: the early development of immune system cells called B cells.

B cells are formed in the bone marrow and produce antibodies. Antibodies are generated from the cutting and splicing of immunoglobulin genes early in B-cell development, and have the potential to develop strong and highly specific affinity for different pathogens. When an infectious pathogen (a disease-causing agent) enters the body, B cells are activated and release antibodies into the bloodstream to combat the pathogen. When antibodies encounter the pathogen, they bind to it, rendering it incapable of causing further harm. Antibody molecules also serve as receptors on the surface of B cells.

The problem occurs when the random cutting and splicing of immunoglobulin genes results in an antibody that recognizes a component of one's own body. While the body has a built-in mechanism to correct these errant cells, the NIAMS researchers discovered this doesn't always work the way it was intended. "What happens is that, if the body ever produces a cell with a self-reactive antibody molecule, that cell will get arrested in development at the point where it is actually combining and creating an antibody receptor," says Rafael Casellas, Ph.D., an investigator in NIAMS's Genomic Integrity and Immunity Group. Often, rather than killing off the cell, the body edits ?or corrects ?the receptor, like one might edit a paper, he says. In normal circumstances, this new, good receptor replaces the bad one, but what Casellas and Dr. Patrick C. Wilson of the Oklahoma Medical Research Foundation found was
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Source:NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases


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