JEM: Reveals the molecular mechanisms by which the body produces memory B cells and maintains a long-lasting immune response

October 19, 2020 // -- The current global COVID-19 epidemic has made vaccines, antibodies and immune responses the subject of daily communication, and now scientists want to know how the body reacts to re-infection months, years, or even decades after the initial immune response. In a study published in the international journal Journal of Student Medicine, scientists from Osaka University in Japan and other institutions have shown that the body's ability to react to infection again requires a protein called Bach2, which regulates the expression of special genes that guide the transformation of active B cells into memory B cells under selective conditions.
Photo Source: Osaka University, like many biological processes in the body, is complex in its immune response, involving several types of cells and proteins that perform step-by-step, precise processes that are unknown.
For example, memory B cells are white blood cells that originate in the lymph nodes or spleen during infection and can stay in the body for many years, and memory B cells react quickly and strongly to re-infection when the body is attacked by the same virus or bacteria.
In contrast, the number of plasma cells in the body is much longer, and it protects the body during the initial infection by producing antibodies, although it can survive long periods of time in the body, and in this study, researcher Kurosaki and colleagues focused on the molecular mechanisms by which the activation of germinal center B cells into memory B cells and plasma cells.
by analyzing the expression of specific protein markers, the researchers were able to identify several types of B-cells, and on the basis of specific markers, the researchers identified a class of B-cell substations that were easily transformed into memory B-cells, and then analyzed mice that were missing the Bach2 protein, Bach. 2 is the transcription factor needed for memory B cell production, and the results show that these mice have some defects in the production of memory B cells, and the absence of Bach2 is related to the decrease of memory B cells and the increase in the expression of mTORC1 protein complex-related genes.
in-depth study, the researchers revealed the importance of mTORC1, Dr Kurosaki said, and we found that mTORC1 signals were less active in memory B cells than in those that were eventually recycled, while in mice where Bach2 was knocked out, inhibiting the activity of mTORC1 (i.e., inducing a decrease in mTORC1 metabolism) may restore the activity of memory B cells and promote the production of gene B cells in mice.
In addition, in wild mouse bodies, artificially reducing the activity of mTORC1 in B cells causes the body to produce more memory white blood cells than in normal conditions, while increasing the activity of mTORC1 has the opposite effect, however, the activity of mTORC1 alone may not explain everything, experimental results show that the unique combination of expression of Bach2 and reduced activity of mTORC1 is necessary to memory B cell production.
Finally, researcher Kurosaki said that understanding the process of producing memory B cells means that manipulating the process can be beneficial to the body, and given the importance of memory B cells in protecting the body from re-infection, inducing them to produce or hopefully help scientists develop effective vaccines that have been effective for years.
() Original source: Takeshi Inoue, Ryo Shinnakasu, Chie Kawai, et al. Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal, Journal of Experiment Medicine (2020). DOI: 10.1084/jem.20200866