It was discovered for the first time that whether the immune system can form high-quality antibodies depends on this enzyme

Japanese experts have identified an essential part of the long-term memory of the immune system, providing useful new details for the design of better vaccines that are suitable for many diseases from COVID-19 to malaria

The immune system is composed of many kinds of cells, but the two types of cells related to the research project of the University of Tokyo are leukocytes, CD4+ follicular helper T cells and B cells

The process of TB cell signal transmission and B cell training occurs in the temporary cell structure called the germinal center in the immune system organs, including the spleen, lymph nodes and tonsils

Michelle SJ Lee, the first author of the study and project assistant professor at the Institute of Medical Sciences at the University of Tokyo, said: "The goal of vaccination is to produce high-quality memory B cells to produce durable antibodies

In a type of white blood cell called B cell, the normal activity of the TBK1 enzyme is essential for the formation of long-term memory in the immune system

"There are many factors to consider when designing a long-acting vaccine, so we should not only focus on the germinal center

However, there is no limit to the number of times you can be bitten by a mosquito and be infected again with the malaria parasite

For Professor Cevayir Coban, this parasite's ability to prevent and evade effective B cells makes malaria an interesting pathogen

"We want to understand the basic principles of the natural immune response

Over the years, the scientific community has determined the multiple roles of the TBK1 molecule

The researchers genetically modified mice that had the non-functional TBK1 gene only in certain types of cells (mainly B cells or CD4+ T cells)

Microscopic images showed that germinal centers were only formed in mice with functional TBK1 in B cells

However, only deleting TBK1 from CD4+ follicular helper T cells has no effect on germinal centers or how mice respond to malaria infection

Further analysis confirmed that in the absence of TBK1, many proteins in immature B cells have abnormal phosphorylation compared with normal immature B cells

Lee said: "This is the first demonstration that TBK1 is essential for B cells to form a germinal center and produce high-quality, mature antibodies

Researchers hope that with more basic knowledge of the remaining mysteries of the immune system, future vaccines can eventually be designed to produce longer-lasting immunity, which may not require multiple doses of vaccines

Coban said: "At present, we can at least say that effective vaccines tailored to produce long-term protective immunity should not reduce the activity of TBK1 in B cells
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Reference: "B cell intrinsic TBK1 is essential for germinal center formation during infection and vaccination in mice" by Michelle SJ Lee, Takeshi Inoue, Wataru Ise, Julia Matsuo-Dapaah, James B.
Wing, Burcu Temizoz, Kouji Kobiyama, Tomoya Hayashi, Ashwini Patil, Shimon Sakaguchi, A.
Katharina Simon, Jelena S.
Bezbradica, Satoru Nagatoishi, Kouhei Tsumoto, Jun-Ichiro Inoue, Shizuo Akira, Tomohiro Kurosaki, Ken J.
Ishii and Cevayir Coban, 15 December 2021, Journal of Experimental Medicine .

DOI: 10.
1084/jem.
20211336