When the body’s B-cell training facility stays open after hours — ScienceDaily

Understanding how germinal centers work is therefore important for understanding immunity and developing more effective vaccines.New research now cell It reveals why some germinal centers persist for months instead of weeks, providing useful insights for future vaccine design.

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Germinal centers form in the body’s lymphoid tissue shortly after vaccination or infection. Once in the germinal center, B cells undergo rapid mutation and undergo a process of natural selection such that only those B cells with antibodies that most effectively bind their target antigen survive. These superior B cells become either plasma cells, antibody factories that secrete large amounts of antibodies into the serum, or memory B cells that patrol the body for signs of a return of the pathogens they evolved to fight. .

“The goal of germinal centers is to generate and export high-affinity plasma cells and memory B cells,” said Renan VH de Carvalho, a postdoctoral fellow in the Gabriel D. Victor lab at The Rockefeller University. I’m here.

In mice, most germinal centers closed after a few weeks, achieving the goal of producing high-affinity B cells. However, those that form in response to certain respiratory infections, such as influenza, can remain active for more than six months, about a quarter of a mouse’s normal lifespan. De Carvalho and his colleagues wanted to understand why these germinal centers are so long-lived and what exactly happens inside them.

In this study, the researchers first infected mice with the influenza virus and the SARS-CoV-2 virus, waited for them to form germinal centers, and spent 24 weeks extracting antibody genes from B cells harvested from those centers. determined the sequence. Surprisingly, rather than continuously evolving at a steady pace, antibody optimization peaked after 12 weeks, followed by a clear regression even though the center remained active. I found Researchers later discovered that this puzzling decline was due to the continuous introduction of unevolved ‘naive’ B cells into germinal centers.

As the weeks turned into months, a more complete picture began to form. Founder B cells, which initially seeded long-lived germinal centers, were gradually replaced by naive ones, so that only a small fraction of late germinal centers initiated their B-cell progeny.

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These recruits did not behave like the original B cells in germinal centers. Subsequent experiments showed that naive B cells also evolved within germinal centers but did not produce antibodies capable of binding to influenza or SARS-CoV2 antigens.

“Previously, we thought of infection-induced germinal centers as a single response that targets antigens from specific pathogens,” says de Carvalho. “Apparently not, at least not for these long-lived germinal centers.”

However, the few original B cells that remained in the field were sufficient to generate efficient immunity against the original pathogen. The researchers found that when mice were re-exposed to influenza antigens 3 months after the initial infection (effectively mimicking repeated infections or booster shots), many of the memory B cells that began pumping out antibodies were found in a small number of founders. proved to be descendants of Cells that have remained in germinal centers for many months and are not simple replacements.

“They make up a small fraction of the total number of cells later on, but the founder cells that stay in the germinal center for a long time still have a job,” says de Carvalho. How well it works, and whether naive recruits cramp its style and reduce its effectiveness remains to be seen. Future research from Victor Labs will address this issue.

On the other hand, this finding has already impacted the general understanding of how germinal centers work. Understanding the dynamics between founder and naïve B cells will enable researchers to exploit long-lived germinal centers to develop more effective antibodies against dangerous respiratory viruses such as influenza and SARS-CoV-2. may help produce

“Ongoing invasion of germinal center structures by a continuous wave of B cells may prove to be an important factor in predicting germinal center outcome, perhaps well beyond this particular influenza model.” there is,” says Victora. Induce germinal centers to produce the necessary antibodies. “