Navigation Links
IRCM scientists find a novel research model for the study of auto-immune diseases

Montral, July 3, 2013 A team of researchers at the IRCM, led by Dr. Javier M. Di Noia in the Immunity and Viral Infections research division, discovered a novel research model for the study of auto-immune diseases. The Montral scientists are the first to find a way to separate two important mechanisms that improve the quality of antibodies. This study was featured in a recent issue of The Journal of Immunology.

Dr. Di Noia's team studies B cells, a group of white blood cells known as lymphocytes whose main function is to produce antibodies to fight against antigens. Antibodies are proteins used by the immune system to identify and neutralize foreign objects (antigens), such as bacteria and viruses, by precisely binding to them, thus making them an essential part of the immune system. Antibodies can come in different varieties (or classes), which perform different roles and adapt the immune response to eliminate each different toxin or pathogen they encounter. The body's great diversity of antibodies therefore allows the immune system to specifically neutralize an equally wide variety of antigens.

"Our project focused on two mechanisms that produce this wide variety of antibodies," says Dr. Di Noia, Director of the Mechanisms of Genetic Diversity research unit at the IRCM. "Because both processes are initiated by the same enzyme known as AID (activation-induced deaminase), it had previously been very difficult to study them separately. We were able to identify, for the first time, a mouse model in which the mechanisms could be analyzed independently during an acute immune response."

The two mechanisms in question are known as class switching and affinity maturation. Class switching is the process that allows a B cell to produce different classes of antibodies, so that a single antibody can be used by several different parts of the immune system. Affinity maturation, on the other hand, is the process by which B cells produce antibodies with increasingly stronger bonds to antigens during an immune response.

"Since eliminating AID would in turn completely eliminate affinity maturation and class switching, we focused on an enzyme called UNG, which is also involved in both processes," adds Astrid Zahn, research associate in Dr. Di Noia's laboratory and first author of the study. "When we analyzed mice lacking the UNG gene, we found that affinity maturation was normal but class switching was strongly reduced during acute immune responses, such as the response to immunization and against a viral infection."

"While over 100 AID-deficient patients have been identified, it is striking that only a handful of patients are known to be UNG-deficient," explains Dr. Zahn. "Our study, which shows that chronic antibody responses (those to environmental antigens) remain nearly normal without UNG, can explain why most UNG-deficient individuals are not detected among immunodeficient patients. Nevertheless, because we also found that acute antibody responses were significantly affected, we suspect that UNG-deficient people will, for example, respond very poorly to vaccination. In addition, as this work was conducted as part of a larger ongoing investigation of the complex relationship between AID and UNG, we believe that UNG might possibly act as a tumour-suppressor in B-cell lymphomas."

"Until now, it was difficult to study the relative importance of class switching and affinity maturation, and the impact of these two mechanisms on immune responses," concludes Dr. Di Noia. "Our study provides a novel model to study the contribution of these mechanisms in certain auto-immune diseases such as lupus and rheumatoid arthritis, or some infections like influenza."


Contact: Julie Langelier
Institut de recherches cliniques de Montreal

Related medicine news :

1. Scientists solving the mystery of human consciousness
2. Scientists uncover multiple faces of deadly breast cancer
3. Scientists identify major source of cells defense against oxidative stress
4. Scientists tailor cell surface targeting system to hit organelle ZIP codes
5. Scientists rewrite rulebook on breast cancer in landmark global study
6. Warwick scientists uncover how checkpoint proteins bind chromosomes
7. NIH scientists link quickly spreading gene to Asian MRSA epidemic
8. Joslin scientists identify important mechanism that affects the aging process
9. Scripps Research scientists show how memory B cells stay in class to fight different infections
10. Scientists Map Melanomas Genome
11. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
Post Your Comments:
(Date:6/24/2016)... ... ... A recent article published June 14 on E Online details ... to state that individuals are now more comfortable seeking to undergo not only the ... and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians (BHP) notes ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is ... associated with chronic pain and the benefits of holistic treatments, Serenity Recovery Center ... suffering with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary ... Dallas that it will receive two significant new grants to support its work ... marked its 25th anniversary by recognizing patients, medical professionals and scientists for their ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. Amanda Cheng, an ... Dr. Cheng has extensive experience with all areas of orthodontics, including robotic Suresmile ... orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. It can ...
(Date:6/24/2016)... NY (PRWEB) , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin ... companies that call for a minimum wage raise to $12 an hour by 2020 and ... This will restore the lost value of the minimum wage, assure the wage floor does ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016   Pulmatrix, Inc ... company developing innovative inhaled drugs, announced today that it ... Russell Investments reconstituted its comprehensive set of U.S. ... "This is an important milestone for Pulmatrix," said ... increase shareholder awareness of our progress in developing drugs ...
(Date:6/23/2016)... , June 23, 2016 Any dentist who has ... of the current process. Many of them do not even ... technical difficulties and high laboratory costs involved. And those who ... it at such a high cost that the majority of ... Dr. Parsa Zadeh , founder of Dental Evolutions ...
(Date:6/23/2016)... 23, 2016 Capricor Therapeutics, ... a biotechnology company focused on the discovery, development ... patient enrollment in its ongoing randomized HOPE-Duchenne clinical ... 50% of its 24-patient target. Capricor expects the ... quarter of 2016, and to report top line ...
Breaking Medicine Technology: