Experts in Japan have identified a fundamental part of the immune system’s long-term memory, providing a useful new detail in the pursuit to design better vaccines for diseases, ranging from COVID-19 to malaria.

The immune system is made of many cell types, but the two types relevant for this University of Tokyo research project are white blood cells called CD4+ follicular helper T cells and B cells. After the body recognizes an infection, the follicular helper T cells release chemical signals that cause immature B cells to learn and remember what pathogens to attack. This process of T-to-B cell signaling and B cell training occurs within a temporary cell structure called the germinal center in organs of the immune system, including the spleen, lymph nodes and tonsils. Memory B cells developed within the germinal center memorize a pathogen the first time it infects you and then if it ever gets into your body again, the mature, trained memory B cells attack it by inducing antibody production before the pathogen can multiply, saving you from feeling sick a second time.

«A goal of vaccination is to produce high-quality memory B cells for long-lasting antibody production,» said Project Assistant Professor Michelle S. J. Lee from the UTokyo Institute of Medical Science, first author of the recent publication.

«There are many factors to consider when designing vaccines for long-lasting immunity, so we should not focus only on the germinal center alone. But if you don’t have a functional germinal center, then you will be very susceptible to reinfection,» said Lee.

However, there is no limit to the number of times you can be bitten by mosquitoes and reinfected by the malaria parasite. Somehow, malaria parasites escape memory B cells. Although children are more likely to die from malaria than adults, some people can become severely ill despite any number of previous malaria infections.

This ability of the parasite to prevent and evade effective B cells is what makes malaria an interesting pathogen for Professor Cevayir Coban, who leads the Division of Malaria Immunology at the UTokyo Institute of Medical Science and is last author of the research paper with Lee and collaborators at Osaka University.

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