Researchers at the Institute of Biophysics of the Chinese Academy of Sciences and the University of Cambridge have developed a new technology that can help identify certain proteins on immune cells that are critical to combating human invaders.
When our bodies are attacked by foreign objects such as bacteria and viruses, our immune system carefully arranges a complex comeback strategy involving many separate parts. An important component of this response is a class of cells called B-lymphocytes, which are at the forefront of our defense system because it recognizes and attempts to neutralize invaders.
B lymphocytes produce a protein called a B cell receptor on the surface. This receptor recognizes and attaches to antigen molecules of invading organisms. This triggers the division of B lymphocytes and releases specialized proteins called antibodies that neutralize the antigen.
Many aspects of this process are still not well understood. One reason is because B cell receptors are not isolated in the B lymphocyte surface. Instead, it forms a local cluster along with many "molecular neighbors." It is these local interactions that control lymphocyte division and replication and determine the strength of the antibody response. If these interactions are better understood, it may ultimately lead us to better control the immune response, as in vaccine development. However, the molecular connections within the cluster are relatively weak, so it is technically difficult to identify them.
An international team of scientists from the Institute of Biophysics of the Chinese Academy of Sciences, the Department of Biochemistry at the University of Cambridge and the Cambridge Proteomics Center has developed this new technology to detect some of these molecules. The experiment was mainly completed by Li Xuewen of the Graduate School of Biophysics of the Chinese Academy of Sciences (Li Xue-Wen) and Dr. Jo Rees of the University of Cambridge. The results of the study were published in the Journal of Biological Chemistry, May 23, 2014. This method allows proteins that are close to the B cell receptor to be chemically labeled in a manner that makes them easier to separate. The labeled molecules can then be identified by a method called mass spectrometry.
In this preliminary original theory experiment, the researchers looked at the B cell receptors on the surface of chicken B lymphocytes and found some molecules that have not been considered to be involved in the regulation of receptors so far. They found that these molecules bind to receptors and activate a class of proteins called integrins, which are known to play an important role in the response of B lymphocytes to antigens. The same molecule is present on the surface of human B lymphocytes, and drugs that are effective against integrins have been used to modulate immune responses. Therefore, the long-term significance of this work may lie in the discovery of new drug targets for immune regulation.
Professor Sarah Perrett of the Institute of Biophysics of the Chinese Academy of Sciences said: "With this technique, we have solved a particularly challenging problem: How do we identify weak and transient, but potentially important interactions between membrane proteins?"
Dr. Tony Jackson of the Department of Biochemistry at the University of Cambridge said: "There are many problems in cell biology. We want to find proteins that are concentrated on the cell surface. Our methods can also be applied to these situations. Therefore, for academia and industrial biology. For many researchers in the medical world, it should be very meaningful."
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