Diversity may be the spice of life, but it’s also the key to an effective immune system, as B lymphocytes rely on extensive recombination to shuffle their antibody-coding genes to produce molecules that can recognize a diverse array of potential threats.
Antibodies with established targets can also undergo further alterations to modulate the immune response that they trigger upon antigen binding. Known as ‘class switch recombination’ (CSR), this process relies on activation-induced cytidine deaminase (AID), an enzyme that induces major rearrangements in antibody-coding loci.
Unregulated, AID can generate cancer-causing genomic rearrangements, and a team led by Tasuku Honjo and Hitoshi Nagaoka at the University of Kyoto, with Sidonia Fagarasan’s group at the RIKEN Research Center for Allergy and Immunology in Yokohama, recently set about exploring the mechanisms that help constrain expression of the Aicda gene.
“AID is tightly regulated in activated B cells and speculated to be a B cell-specific factor—however, the Aicda promoter is not lymphocyte specific,” says Thinh Huy Tran, lead author of the team’s recent article in Nature Immunology1. Comparison of the mouse and human versions of this promoter revealed four discrete segments that had been closely conserved throughout evolution. To assess their contributions to gene specificity, the researchers generated artificial promoters consisting of various subsets of these conserved regions, which they used to regulate a bioluminescence-producing ‘reporter’ gene in cultured lymphocytes.
They found that two of these four segments directly contribute to specificity. ‘Region 2’ contains binding sites for transcription factors known to guide B lymphocyte development, but also contains sequences that strongly inhibit Aicda expression. The other promoter segment, ‘region 4’, appears to participate in the strong induction of this gene in response to signaling factors that trigger CSR in vivo.
“Our results demonstrate for the first time that two separate regions contribute together to regulating Aicda expression, in which silencers are derepressed by B lineage-specific and stimulation-responsive enhancers,” says Tran. “The negative factors that restrict Aicda expression might contribute to retaining genomic stability, while region 4 is essential for Aicda response in B cells to environmental stimulation ... and is critical to generate antibody diversification.”
The investigators are now examining the individual importance of these various putative Aicda regulators, but also intend to further explore the bigger picture of the effects of AID dysregulation. “We plan to investigate the correlation between Aicda expression levels with mutation frequency in non-immune genes ... and the role of AID in tumor development,” says Tran.
The corresponding author for this highlight is based at the Laboratory for Mucosal Immunity, Research Center for Allergy and ImmunologyJournal information
Saeko Okada | Research asia research news
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction