Immunity system complexity: ramping up B cells (Introduction)

by David Turell , Friday, December 23, 2022, 18:43 (491 days ago) @ David Turell

In specialized germinal centers:

https://medicalxpress.com/news/2022-12-body-cell-grounds-stay-hours.html

"If B cells are the munitions factories of the immune system, manufacturing antibodies to neutralize harmful pathogens, then the tiny biological structures known as germinal centers are its weapons-development facilities. Formed in response to infection and vaccination, these microscopic training grounds allow B cells to perfect the antibodies they deploy against specific viruses and bacteria. (my bold)

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"Germinal centers form in the body's lymphatic tissues shortly after vaccination or infection. Once inside a germinal center, B cells undergo rapid mutations and, through a process of natural selection, only B cells with antibodies that most effectively bind to their target antigens survive. These superior B cells then become either plasma cells, antibody factories that secrete copious amounts of antibodies into serum, or memory B cells, which patrol the body for signs of return of the pathogen they evolved to fight.

"The goal of the germinal center is to generate high-affinity plasma cells and memory B cells, that it then exports," says Renan V.H. de Carvalho, a postdoctoral fellow in the laboratory of Gabriel D. Victora at The Rockefeller University.

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"As weeks turned into months, a more complete picture began to form: the founder B cells that had initially seeded the long-lived germinal centers were being gradually replaced by naïve ones, so that only a tiny fraction of late germinal centers were made of the descendants of the B cells that started them.

"These new recruits did not behave like the original B cells in the germinal center. Subsequent experiments showed that, while the naïve B cells also underwent evolution inside the germinal centers, they did not produce antibodies that could bind to flu or SARS-CoV2 antigens.

"We used to think of infection-induced germinal centers as a single reaction targeting antigens from a particular pathogen," de Carvalho says. "Apparently it's not, at least in the case of these long-lived germinal centers."

"But the few original B cells that remained on site were enough to produce efficient immunity against the initial pathogen. When the researchers re-exposed the mice to flu antigens 3 months after they were first infected—effectively mimicking a repeat infection or booster shot—they demonstrated that many of the memory B cells which began pumping out antibodies were descended from the few founder cells that lingered in germinal centers for many months, and not their naïve replacements.

"'Even though they constitute a small fraction of the total number of cells later on, the founder cells that stay in the germinal center for a long time are still doing their job," de Carvalho says. But just how well those founder B cells do their jobs, and whether naïve recruits cramp their style and reduce their efficacy, remains to be seen. Future studies from the Victora lab will address this question."

Comment: it is logical to design immediate short-term defenses and carry the memory bank of B-cell-forming antibodies into the future