immune reaction occurs, some special areas— germinal centers (germinal centers)—will be formed in the lymph nodes and the spleen. The germinal center is like a classroom where immune cells gather to learn how to mount a long-lasting antibody response to pathogens. In some people with severe COVID-19 infection, no germinal centers are formed in the lymph nodes and spleen.
This article is original to the Translational Medicine Network. Please indicate the source for reprinting.
Author: kope
Understanding how the germinal center works is crucial to understanding immunity and developing more effective vaccines . Now, a new study in the journal Cell reveals why some germinal centers persist for months rather than weeks, providing insights that could inform future vaccine design. In recent years, people have paid more and more attention to the research of immune-related diseases, and have successively proposed a variety of immunotherapy methods.
produces the antibodies required for
B cell clones induced by influenza virus or SARS-CoV-2 infection in mice infected by respiratory viruses and identified clonal replacement as a potential limiting factor in the development of highly mutated antibodies within these structures. The body's acquired immune response is mainly composed of cellular immune responses mediated by activation of T lymphocytes and humoral immune responses induced by activation of B lymphocytes. Among them, B lymphocyte mainly exerts immunomodulatory functions by producing specific antibodies. The formation of specific antibodies mainly comes from the germinal center (GC). Abnormal activation of B lymphocytes in the germinal center can trigger a variety of pathological reactions and even induce malignant lymphoma and other diseases.
"Continuous waves of B cells invading ongoing germinal center structures may be an important factor in predicting germinal center outcomes, possibly well beyond this specific influenza model," Victora said, "and may give us insight into how germinal centers are induced to produce the antibodies we need.
Peak after 12 weeks
In biology , no story is more intriguing than the complex process of B cell and antibody production. This is a story about mathematics, a story about genetics , and an epic that reveals how thousands of small-sized antibody armies control various disease-causing substances. Shortly after vaccination or infection, germinal centers form in the body's lymphoid tissue. Once in the germinal center, B cells undergo rapid mutation and, through a process of natural selection, only those with the antibodies that most efficiently bind their target antigens B cells can survive. These superior B cells then either become plasma cells , antibody factories that secrete large amounts of antibodies into the serum, or memory B cells that patrol the body looking for signs of the return of the pathogens they evolved to fight.
In mice, most germinal centers shut down after a few weeks, achieving the goal of generating high-affinity B cells. But those responding to certain respiratory infections, including influenza, can stay in business 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 the study, the researchers first infected mice with influenza and SARS-CoV-2 viruses, waited for them to form germinal centers, and then sequenced the antibody genes of B cells harvested from these centers over 24 weeks. To their surprise, they found that instead of continuing at a steady rate, antibody optimization peaked after 12 weeks and then significantly regressed, even though the centers were still active. researchers later discovered that this puzzling decline was due to the continuous introduction of unevolved "naïve" B cells into the germinal centers.
Fighting respiratory viruses
A small number of naive B cells are sufficient to generate effective immunity against the initial pathogen. When the researchers re-exposed mice to influenza antigens 3 months after their initial infection, effectively mimicking a superinfection or booster injection, they demonstrated that many of the memory B cells that began pumping out antibodies were descendants of the few founder cells that lingered around the germinal centers for months, rather than their naive replacements.
"Even though they later make up only a small fraction of the total number of cells, the founder cells that remain in the germinal center for a long time are still functioning," de Carvalho said. At the same time, these findings are already having implications for our general understanding of how germinal centers operate. Understanding the dynamics between founders and naïve B cells could help researchers harness long-lived germinal centers to produce more effective antibodies against dangerous respiratory viruses like influenza and SARS-CoV-2.
Reference:
https://doi.org/10.1016/j.cell.2022.11.031
https://www.news-medical.net/news/20221 223/Study-reveals-why-some-germinal-centers-persist-for-months-rather-than-weeks.aspx
Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital.
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