Scientists develop method to track immune system enzyme in live animals

May 17, 2007
Mouse Plasma Cells are Tagged with Yellow Fluorescent Protein
In this picture of intestinal villi from one of the new mouse strains, plasma cells are tagged with yellow (green-appearing) fluorescent protein. Credit: National Institute of Arthritis and Musculoskeletal and Skin Diseases

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 regulated or deregulated is that there has not been an easy way to visualize the enzyme’s action in a living animal — until now.

To address this issue, Dr. Casellas and his colleagues created transgenic mice that had a green fluorescent protein derived from jellyfish fused to the AID enzyme. In these transgenic animals, B cells express the tagged enzyme during the immune response. In a second mouse strain, Casellas and coworkers expressed permanently a yellow fluorescent protein in the progeny of germinal center B cells. "Thanks to these new mouse models, we can track in live animals whenever the AID enzyme is active as well as the result of that activity," says Casellas. Scientists can also cross these new mouse strains with mice predisposed to B-cell tumors or autoimmunity to see differences in enzyme expression in health and disease.

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Explore further: Research team unlocks secrets of Ebola

Related Stories

Research team unlocks secrets of Ebola

November 16, 2017
In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in Cell Host and Microbe, a scientific team led by the University of Wisconsin-Madison has ...

Protein regulates vitamin A metabolic pathways, prevents inflammation

October 23, 2017
A team of researchers from Case Western Reserve University School of Medicine have discovered how uncontrolled vitamin A metabolism in the gut can cause harmful inflammation. The discovery links diet to inflammatory diseases, ...

Solving of a decade long mystery could help in fight against tuberculosis

November 1, 2017
Scientists have solved a decade-old mystery that could eventually lead to the development of earlier treatments for one of the world's deadliest diseases, which affects up to 2 billion people.

How and why blood clots shrink

November 9, 2017
Blood clotting is the "Jekyll and Hyde" of biological processes. It's a lifesaver when you're bleeding, but gone awry, it causes heart attacks, strokes and other serious medical problems. If a clot grows too big, pieces dislodged ...

Likely new treatment target identified for diabetic retinopathy

October 10, 2017
In oxygen-compromising conditions like diabetes, the body grows new blood vessels to help, but the result is often leaky, dysfunctional vessels that make bad matters worse.

Study finds less extensive damage in young female mice from chemotherapy-induced kidney injury

September 6, 2017
Young females may have the greatest level of protection against acute kidney injury (AKI) caused by the chemotherapy drug Cisplatin, commonly used to treat lung, ovarian, bladder and stomach cancer. Nearly a third of all ...

Recommended for you

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.