Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Autoimmune Diseases Research Model Developed to Clarify Antibody Mechanisms

By BiotechDaily International staff writers
Posted on 21 Jul 2013
Canadian scientists have devised a unique research model for the study of autoimmune diseases. The Montréal scientists are the first to find an approach to better understand two significant processes that enhance the quality of antibodies.

This study, conducted by researchers from the l'Institut de Recherches Cliniques de Montréal (IRCM; QB, Canada), led by Dr. Javier M. Di Noia in the immunity and viral infections research division, was published in the June 15, 2013, issue of the Journal of Immunology.

Dr. Di Noia’s team is evaluating B cells, a group of white blood cells known as lymphocytes whose major task is to make antibodies to fight against antigens. “Our project focused on two mechanisms that produce this wide variety of antibodies,” said 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 processes being studied are known as class switching and affinity maturation. Class switching is the mechanism that allows a B cell to generate diverse 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,” added Astrid Zahn, research associate in Dr. Di Noia’s laboratory and first author of the study. “When we analyzed mice lacking the UNG [uracil-DNA glycosylase] 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,” explained 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 tumor-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,” concluded Dr. Di Noia. “Our study provides a novel model to study the contribution of these mechanisms in certain autoimmune diseases such as lupus and rheumatoid arthritis, or some infections like influenza.”

Related Links:

l'Institut de Recherches Cliniques de Montréal



Channels

Genomics/Proteomics

view channel
Image: Many molecular biology studies begin with purified DNA and RNA extracted from complex environments such as the human gut (Photo courtesy of Los Alamos [US] National Laboratory).

New Metagenomics Analysis Tool Reduces False Discovery Rates

Genomic researchers recently described a novel new tool for analyzing the complex data generated during DNA screens of mixed populations of organisms such as the human gut microbiome. DNA screening... Read more

Drug Discovery

view channel
Image: Wafers like the one shown here are used to create “organ-on-a-chip” devices to model human tissue (Photo courtesy of Dr. Anurag Mathur, University of California, Berkeley).

Human Heart-on-a-Chip Cultures May Replace Animal Models for Drug Development and Safety Screening

Human heart cells growing in an easily monitored silicon chip culture system may one day replace animal-based model systems for drug development and safety screening. Drug discovery and development... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

“Softer” Mass Spec Techniques Gain Advantage in Biomarker Discovery

Two mass spectrometry (MS) technologies, MALDI and DESI, are increasing in applications as their effectiveness is established, according to Kalorama Information (New York, NY, USA) in its report “Proteomics Markets for Research and IVD Applications (Mass Spectrometry, Chromatography, Microarrays, Electrophoresis, Immunoassays,... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.