National University Corporation Okayama University
[Okayama University] Aiming to improve immunity by elucidating the mechanism by which highly functional antibodies are produced in the body
Okayama University is a comprehensive university-type national university corporation with 10 faculties, 1 program, 8 graduate schools, 4 research institutes, an affiliated hospital, and an affiliated school.
This time, “FOCUS ON” was published on September 29, 2022 to introduce the latest research results in an easy-to-understand manner. Please take a look!
October 2, 2022
National University Corporation Okayama University
https://www.okayama-u.ac.jp/
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-Points of announcement-
Antibodies produced in the body bind to harmful substances such as viruses and cancer cells and activate the immune system to eliminate them.
We are elucidating the mechanisms by which the ability of antibodies to identify and eliminate pathogens is gradually strengthened after infection.
Clarifying the mechanism by which highly functional antibodies are produced in the body will lead to the development of pharmaceuticals for the rapid production of highly functional antibodies.
◆Presenter
Masaki Magari Assistant Professor, Department of Integrated Science for Health Systems, Faculty of Science, Okayama University
◆Overview
Our bodies are equipped with an excellent immune system to protect ourselves from pathogens such as viruses and bacteria, as well as cancer cells.
Antibodies are proteins that play an important role in the immune system to identify and eliminate pathogens and cancer cells. The production of large amounts of highly recognizable antibodies in the body is important in order to protect oneself from infectious diseases and other diseases, and is also known as the principle of vaccines. A group led by Assistant Professor Masaki Mugi of the Faculty of Science, Okayama University, has been the first in the world to extract regulatory cells that regulate the function of
antibody-producing B cells from the body and stably culture them. have succeeded in This time, together with Miku Nishioka (then) of the Graduate School of Integrated Sciences in Health Systems, and others, we used cell culture technology to investigate how regulatory cells regulate the function of B cells.
As a result, we conducted a comprehensive search for molecules expressed by regulatory cells, and discovered molecules that are expressed by regulatory cells and may enhance the antibody’s ability to discriminate and eliminate.
In the future, by examining the functions of the identified molecules in the body, it may be possible to apply them to the development of technologies that produce high performance in a short period of time. The results of this research were published in “FEBS Letters” on August 11, 2022.
◆ Introduction
Inside the body, harmful substances (antigens ) is equipped with the immune system to eliminate Antibodies are important proteins for our health that identify harmful substances by directly binding to them and activate the immune system. It is also known that the ability of this antibody to eliminate harmful substances increases with time after infection.
In addition, the immune system has the ability to remember antigens that have been recognized once, and highly functional antibodies are immediately produced in the event of reinfection. Therefore, clarifying the mechanism by which highly functional antibodies are produced in the body will lead to technological development for efficient production of powerful antibodies that can eliminate harmful substances. Therefore, I started researching the mechanism by which antibodies are produced in the body.
◆ Background
Antibodies are produced from B cells, a type of lymphocyte. B cells that recognize pathogens such as viruses release large amounts of antibodies that bind to pathogens for host defense. At that time, it is known that the ability of antibodies to bind to pathogens (clearance ability) increases over time.
This series of B cell responses is based on complex instructions from various cells (Fig. 1). Until now, the existence of a central group of cells (regulatory cells) that control antibody production and functionalization of B cells was known. However, it has been difficult to isolate regulatory cells because they exist in only a small number in the body.
Due to this problem, it was difficult to use a cell culture system to analyze in detail the complex exchange of information between B cells and the cells that control the responses of B cells that occur in the body.
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Figure 1. Antibody production mechanism of B cells
◆Research content and achievements
Previously, Assistant Professor Mutsu’s group used a special cell culture method using collagen gel to generate a group of cells (control cells) necessary for B cells to produce high-performance antibodies from mouse lymph nodes. In addition, we succeeded in stably culturing control cells in vitro (Fig. 2). This has made it easier to analyze the properties of regulatory cells, making it possible to elucidate the interactions between B cells and regulatory cells in vitro.
After that, using this unique cell culture technology, we have clarified how regulatory cells control the reactions of B cells. Recently, as one of the results of this research, together with Miku Nishioka (then graduate student), we discovered that a group of molecules expressed by regulatory cells that recognize the invasion of pathogens directly and indirectly regulates the response of B cells. We identified the existence of a molecule that has the potential to do so (Reference 1). Furthermore, when we artificially produced this molecule and investigated its function, we showed the possibility of promoting the high functionality of antibodies in B cells.
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Figure 2. Control cells isolated from mouse lymph nodes
◆ Perspective
“Vaccination is considered an effective means against infectious diseases.” Vaccines produce large amounts of antibodies in the body that can bind to pathogens. Understanding and utilizing the antibody production mechanism in the body will lead to technology that can induce a large amount of highly functional antibodies in a short time during vaccination.
Until now, we have mainly focused on the analysis of regulatory cells in vitro, but in the future, we would like to analyze the dynamics of the molecules identified this time in the body, which will lead to the development of methods for enhancing immunity. I’m here.
◆ Document 1
Paper title: The immunoreceptor SLAMF8 promotes the differentiation of follicular dendritic cell-
dependent monocytic cells with B cell-stimulating ability.
Published paper: FEBS Letters
Authors: Masaki Magari, Miku Nishioka, Tomomi Hari, Sayaka Ogawa, Kaho Takahashi, Naoya Hatano,
Naoki Kanayama, Junichiro Futami, Hiroshi Tokumitsu
DOI: 10.1002/1873-3468.14468
URL: https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14468 FOCUS ON: Aiming to improve immunity by elucidating the mechanism by which highly functional antibodies are produced in the body
https://www.okayama-u.ac.jp/up_load_files/press_r4/press20220928-2.pdf ◆ Reference
・Graduate School of Integrated Sciences in Health Systems, Okayama University https://www.gisehs.okayama-u.ac.jp/
・Graduate School of Integrated Science and Technology, Okayama University Cell Function Design Laboratory
https://www.okayama-u.ac.jp/user/saibou/index.html
・Okayama University Faculty of Engineering
https://www.engr.okayama-u.ac.jp/
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Okayama University Tsushima Campus (Kita Ward, Okayama City) ◆ Inquiries regarding this matter
Masaki Magari Assistant Professor, Department of Integrated Science for Health Systems, Faculty of Science, Okayama University
3-1-1 Tsushimanaka, Kita-ku, Okayama City, Okayama Prefecture 700-8530, Okayama University Tsushima Campus Engineering Building No. 6, 3rd Floor
TEL: 086-251-8199
https://www.okayama-u.ac.jp/user/saibou/index.html
-Inquiries regarding Okayama University’s industry-academia-government collaboration-
Okayama University Organization for Research Promotion Headquarters for Industry-Academia-Government Collaboration
1-1-1 Tsushimanaka, Kita-ku, Okayama City, Okayama Prefecture 700-8530 Okayama University Tsushima Campus Main Building 1F TEL: 086-251-8463
E-mail: sangaku◎okayama-u.ac.jp
https://www.orsd.okayama-u.ac.jp/
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