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Scientists Develop Method to Track Immune System Enzyme in Live Animals

Scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health have created two mouse strains that will permit researchers to trace, in a live animal, the activity of an enzyme believed to play a crucial role both in the normal immune response as well as autoimmunity and B cell tumor development. Their report appears in the Journal of Experimental Medicine.

The enzyme, known as activation-induced cytidine deaminase or AID (which has no relation to the AIDS virus), is expressed by B cells, which are produced in the bone marrow and are responsible for making antibodies that attack foreign invaders such as viruses and bacteria. The enzyme enables the cells to respond with precision to the almost limitless types of invaders the body may encounter. Unfortunately, it also has a down side.

B cells constantly scan the body for foreign invaders, explains Rafael Casellas, Ph.D., an investigator in NIAMS Molecular Immunology and Inflammation Branch and lead author of the paper. As B cells encounter foreign antigens from viruses, bacteria or allergens, they migrate to germinal centers specialized microenvironments in tonsils, spleen and lymph nodes.

Within germinal centers, B cells divide extensively and express the AID enzyme, which causes random mutations and recombination in the cells immunoglobulin (antibody) genes. For the most part, these genetic changes are beneficial because they enable B lymphocytes to attack and stop the invader. In some cases, however, AID-dependent alterations in the genetic material of B cells can also lead to unwanted results such as autoimmunity and development of B cell tumors, as in the case of Burkitt lymphoma.

It becomes crucial that we comprehend how AID is regulated during the normal immune response as well as in tumorigenesis and autoimmunity, says Casellas. The problem with understanding how AID is regu
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